22,495 results match your criteria Molecular and Cellular Biology[Journal]


Role of SMPD3 during Bone Fracture Healing and Regulation of its Expression.

Mol Cell Biol 2018 Dec 10. Epub 2018 Dec 10.

Faculty of Dentistry, McGill University, Montreal, Quebec, Canada

Sphingomyelin phosphodiesterase 3 (SMPD3), a lipid-metabolizing enzyme present in bone and cartilage, has important roles in the developing skeleton. Using an inducible knockout mouse model, , where was ablated in both expressing chondrocytes and osteoblasts during early skeletogenesis, we showed that SMPD3 deficiency results in delayed extracellular matrix (ECM) mineralization and severe skeletal deformities. Interestingly, in 3-month-old mice, in which was ablated postnatally, only a mild bone mineralization defect was observed. Read More

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http://dx.doi.org/10.1128/MCB.00370-18DOI Listing
December 2018

Yeast Mpo1 is a novel dioxygenase that catalyzes the α-oxidation of a 2-hydroxy fatty acid in an Fe-dependent manner.

Mol Cell Biol 2018 Dec 10. Epub 2018 Dec 10.

Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan

Phytosphingosine (PHS) is the major long-chain base component of sphingolipids in yeast. The PHS metabolic pathway includes a fatty acid (FA) α-oxidation reaction. Recently, we identified the novel protein Mpo1, which is involved in PHS metabolism. Read More

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http://dx.doi.org/10.1128/MCB.00428-18DOI Listing
December 2018
2 Reads

Both a unique motif at the C terminus and N-terminal HEAT repeat contribute to G4 binding and origin regulation by Rif1 protein.

Mol Cell Biol 2018 Dec 3. Epub 2018 Dec 3.

Department of Genome Medicine, Tokyo Metropolitan Institute of Medical Science, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan

Rif1 is a key factor for spatio-temporal regulation of DNA replication. Rif1 suppresses origin firing in the mid-late replication domains by generating replication-suppressive chromatin architecture and by recruiting a protein phosphatase. In fission yeast, the function of Hsk1, a kinase important for origin firing, can be bypassed by Δ, due to the loss of origin suppression. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00364-18
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http://dx.doi.org/10.1128/MCB.00364-18DOI Listing
December 2018
9 Reads

hnRNP Q regulates IRES-mediated translation in neurons.

Mol Cell Biol 2018 Nov 26. Epub 2018 Nov 26.

Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Korea.

Fragile X syndrome (FXS) caused by loss of fragile X mental retardation protein (FMRP) is the most common cause of inherited intellectual disability. Numerous studies show that FMRP is a RNA binding protein that regulates translation of its binding targets and plays key roles in neuronal functions. However, the regulatory mechanism for FMRP expression is incompletely understood. Read More

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http://dx.doi.org/10.1128/MCB.00371-18DOI Listing
November 2018
1 Read

Mutant p53 sequestration of MDM2 acidic domain inhibits E3 ligase activity.

Mol Cell Biol 2018 Nov 19. Epub 2018 Nov 19.

Molecular Oncology Department, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612, USA

Missense p53 mutants often accumulate in tumors and drive progression through gain-of-function. MDM2 efficiently degrades wild type p53, but fails to degrade mutant p53 in tumor cells. Previous studies revealed that mutant p53 inhibits MDM2 auto-ubiquitination, suggesting that the interaction inhibits MDM2 E3 activity. Read More

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http://dx.doi.org/10.1128/MCB.00375-18DOI Listing
November 2018

A novel regulatory axis, CHD1L-miR-486 -MMP2, controls spermatogonial stem cell properties.

Mol Cell Biol 2018 Nov 19. Epub 2018 Nov 19.

Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences; Affiliated Cancer Hospital & Institute of Guangzhou Medical University Xinzao Town, Panyu District, Guangzhou, Guangdong 511436, China

Spermatogonial stem cells (SSCs) are unipotent germ cells and at the foundation of spermatogenesis and male fertility. However, the underlying molecular mechanisms governing SSC stemness and growth properties remain elusive. We have recently identified chromodomain helicase/ATPase DNA binding protein 1-like (Chd1l) as a novel regulator for SSC survival and self-renewal, but how such functions are controlled by Chd1l remains to be resolved. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00357-18
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http://dx.doi.org/10.1128/MCB.00357-18DOI Listing
November 2018
8 Reads

The Phosphorylated Estrogen Receptor Cistrome Identifies a Subset of Active Enhancers Enriched for Direct ER-DNA Binding and the Transcription Factor GRHL2.

Mol Cell Biol 2018 Nov 19. Epub 2018 Nov 19.

McArdle Laboratory for Cancer Research, Department of Oncology and Carbone Comprehensive Cancer Center, University of Wisconsin - Madison, Madison, WI

Post-translational modifications are key regulators of protein function, providing cues that can alter protein interactions and cellular location. Phosphorylation of the estrogen receptor (ER) at serine 118 (pS118-ER) occurs in response to multiple stimuli and is involved in modulating ER-dependent gene transcription. While the cistrome of ER is well established, surprisingly little is understood about how phosphorylation impacts ER-DNA binding activity. Read More

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http://dx.doi.org/10.1128/MCB.00417-18DOI Listing
November 2018
4 Reads

Cancer associated eIF1A mutants impair Rps3 and Rps10 binding and enhance scanning of cell cycle genes.

Mol Cell Biol 2018 Nov 12. Epub 2018 Nov 12.

Dept. of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot 76100, Israel.

Protein synthesis is linked to cell proliferation and its deregulation contributes to cancer. eIF1A plays a key role in scanning and AUG selection and differentially affects translation of distinct mRNAs. Its unstructured N-terminal-tail (NTT) is frequently mutated in several malignancies. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00441-18
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http://dx.doi.org/10.1128/MCB.00441-18DOI Listing
November 2018
2 Reads

Nuclear phosphatidylinositol 5-phosphatase is essential for allelic exclusion of variant surface glycoprotein genes in trypanosomes.

Mol Cell Biol 2018 Nov 12. Epub 2018 Nov 12.

Center for Infectious Disease Research, Seattle, WA 98109, USA

Allelic exclusion of variant surface glycoprotein (VSG) genes is essential for African trypanosomes to evade the host antibody response by antigenic variation. The mechanisms by which this parasite expresses only one of its ∼2,000 VSG genes at a time are unknown. We show that nuclear phosphatidylinositol 5-phosphatase (PIP5Pase) interacts with repressor activator protein 1 (RAP1) in a multiprotein complex and function in the control of VSG allelic exclusion. Read More

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http://dx.doi.org/10.1128/MCB.00395-18DOI Listing
November 2018

Senescent breast luminal cells promote carcinogenesis through IL-8-dependent activation of stromal fibroblasts.

Mol Cell Biol 2018 Nov 5. Epub 2018 Nov 5.

Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre; MBC#03, Riyadh 11211, Saudi Arabia

Aging and stress promote senescence, which has intrinsic tumor suppressor functions and extrinsic tumor promoting properties. Therefore, it is of utmost importance to delineate the effects of senescence-inducers on the various types of cells that compose the different organs. We have shown here that primary normal breast luminal (NBL) cells are more sensitive than their corresponding stromal fibroblasts to proliferative as well as oxidative damage-induced senescence. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00359-18
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http://dx.doi.org/10.1128/MCB.00359-18DOI Listing
November 2018
8 Reads
4.780 Impact Factor

Coordinated regulation of intracellular fascin distribution governs tumor microvesicle release and invasive cell capacity.

Mol Cell Biol 2018 Nov 5. Epub 2018 Nov 5.

Department of Biological Sciences, University of Notre Dame, Notre Dame, IN. 46617.

Tumor cell invasion is one result of the bidirectional interactions occurring between tumor cells and the surrounding milieu. The ability of tumor cells to invade through the extracellular matrix is in part regulated by the formation of a class of protease-loaded extracellular vesicles, called tumor microvesicles (TMVs), which are released directly from the cell surface. Here we show that the actin bundling protein, fascin, redistributes to the cell periphery in a ternary complex with podocalyxin and ezrin, where it promotes TMV release. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00264-18
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http://dx.doi.org/10.1128/MCB.00264-18DOI Listing
November 2018
5 Reads

SNW1 as a novel transcriptional regulator of the NF-κB pathway.

Mol Cell Biol 2018 Nov 5. Epub 2018 Nov 5.

Salk Institute for Biological Studies, La Jolla, California, 92037 USA

The nuclear factor-kappa B (NF-κB) family of transcription factors plays a central role in coordinating the expression of genes that control inflammation, immune responses, cell-proliferation, and a variety of other biological processes. In an attempt to identify novel regulators of this pathway, we performed whole-genome RNAi screens in physiologically relevant human macrophages in response to Lipopolysaccharides and Tumor Necrosis Factor Alpha. The top hit was SNW1, a splicing factor and transcriptional co-activator. Read More

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http://dx.doi.org/10.1128/MCB.00415-18DOI Listing
November 2018
1 Read

Novel Lines of Evidence for the Asymmetric Strand Displacement Model of Mitochondrial DNA Replication.

Authors:
Chih-Lin Hsieh

Mol Cell Biol 2018 Nov 5. Epub 2018 Nov 5.

Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA

The mitochondrial (mt) genome, which consists of 16,569 base pairs of DNA with a cytosine rich light (L) strand and a heavy (H) strand, exists as a multi-copy closed circular genome within the mitochondrial matrix. The machinery for replication of the mammalian mitochondrial genome is distinct from that for replication of the nuclear genome. Three models have been proposed for mtDNA replication, and one of the key differences among them is whether extensive single-stranded regions exist on the H-strand. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00406-18
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http://dx.doi.org/10.1128/MCB.00406-18DOI Listing
November 2018
6 Reads

Hypoxia Restrains Lipid Utilization via Protein Kinase A and ATGL Downregulation through Hypoxia Inducible Factor.

Mol Cell Biol 2018 Nov 5. Epub 2018 Nov 5.

National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea

Oxygen is a key molecule for efficient energy production in living organisms. Although aerobic organisms have adaptive processes to survive in low-oxygen environments, it is poorly understood how lipolysis, the first step of energy production from stored lipid metabolites, would be modulated during hypoxia. Here, we demonstrate that fasting-induced lipolysis is downregulated by hypoxia through the hypoxia-inducible factor (HIF) signaling pathway. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00390-18
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http://dx.doi.org/10.1128/MCB.00390-18DOI Listing
November 2018
2 Reads

IL-8 Activates Breast Cancer-Associated Adipocytes and Promotes Their Angiogenic and Tumorigenic Promoting Effects.

Mol Cell Biol 2018 Nov 5. Epub 2018 Nov 5.

Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, KSA

Increasing evidence supports the critical role of active stromal adipocytes in breast cancer development and spread. However, the mediators and the mechanisms of action are still elusive. We have shown here that cancer-associated adipocytes (CAAs) isolated from 10 invasive breast carcinomas are pro-inflammatory and exhibit active phenotypes, including higher proliferative, invasive and migratory capacities as compared to their adjacent tumor-counterpart adipocytes (TCAs). Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00332-18
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http://dx.doi.org/10.1128/MCB.00332-18DOI Listing
November 2018
15 Reads
4.780 Impact Factor

DDX3 Participates in Translational Control of Inflammation Induced by Infections and Injuries.

Mol Cell Biol 2019 Jan 11;39(1). Epub 2018 Dec 11.

Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan

Recent studies have suggested that DDX3 functions in antiviral innate immunity, but the underlying mechanism remains elusive. We previously identified target mRNAs whose translation is controlled by DDX3. Pathway enrichment analysis of these targets indicated that DDX3 is involved in various infections and inflammation. Read More

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http://aem.asm.org/lookup/doi/10.1128/MCB.00285-18
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http://dx.doi.org/10.1128/MCB.00285-18DOI Listing
January 2019
6 Reads

Specific Modification of Aged Proteasomes Revealed by Tag-Exchangeable Knock-In Mice.

Mol Cell Biol 2019 Jan 11;39(1). Epub 2018 Dec 11.

Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan

The proteasome is the proteolytic machinery at the center of regulated intracellular protein degradation and participates in various cellular processes. Maintaining the quality of the proteasome is therefore important for proper cell function. It is unclear, however, how proteasomes change over time and how aged proteasomes are disposed. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00426-18
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http://dx.doi.org/10.1128/MCB.00426-18DOI Listing
January 2019
3 Reads

Brc1 Promotes the Focal Accumulation and SUMO Ligase Activity of Smc5-Smc6 During Replication Stress.

Mol Cell Biol 2018 Oct 22. Epub 2018 Oct 22.

Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.

As genetic instability drives disease or loss of cell fitness, cellular safeguards have evolved to protect the genome, especially during sensitive cell cycle phases such as DNA replication. Fission yeast Brc1 has emerged as a key factor in promoting cell survival when replication forks are stalled or collapsed. Brc1 is a multi-BRCT protein that is structurally related to the budding yeast Rtt107 and human PTIP DNA damage response factors, but functional similarities appear limited. Read More

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http://dx.doi.org/10.1128/MCB.00271-18DOI Listing
October 2018
5 Reads

A Heterologous Cell Model for Studying the Role of T-Cell Intracellular Antigen 1 in Welander Distal Myopathy.

Mol Cell Biol 2019 Jan 11;39(1). Epub 2018 Dec 11.

Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain

Welander distal myopathy (WDM) is a muscle dystrophy characterized by adult-onset distal muscle weakness, prevalently impacting the distal long extensors of the hands and feet. WDM is an autosomal dominant disorder caused by a missense mutation (c.1362G>A; p. Read More

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http://dx.doi.org/10.1128/MCB.00299-18DOI Listing
January 2019
4 Reads

A Tumor-Promoting Phorbol Ester Causes a Large Increase in APOBEC3A Expression and a Moderate Increase in APOBEC3B Expression in a Normal Human Keratinocyte Cell Line without Increasing Genomic Uracils.

Mol Cell Biol 2019 Jan 11;39(1). Epub 2018 Dec 11.

Department of Chemistry, Wayne State University, Detroit, Michigan, USA

Phorbol 12-myristate 13-acetate (PMA) promotes skin cancer in rodents. The mutations found in murine tumors are similar to those found in human skin cancers, and PMA promotes proliferation of human skin cells. PMA treatment of human keratinocytes increases the synthesis of APOBEC3A, an enzyme that converts cytosines in single-stranded DNA to uracil, and mutations in a variety of human cancers are attributed to APOBEC3A or APOBEC3B expression. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00238-18
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http://dx.doi.org/10.1128/MCB.00238-18DOI Listing
January 2019
8 Reads

Inner Mitochondrial Translocase Tim50 Is Central in Adrenal and Testicular Steroid Synthesis.

Mol Cell Biol 2019 Jan 11;39(1). Epub 2018 Dec 11.

Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.

Adrenal and gonadal mitochondrial metabolic activity requires electrons from cofactors, cholesterol, and a substrate for rapid steroid synthesis, an essential requirement for mammalian survival. Substrate activity depends on its environment, which is regulated by chaperones and mitochondrial translocases. Cytochrome P450 side-chain cleavage enzyme (SCC or CYP11A1) catalyzes cholesterol to pregnenolone conversion, although its mechanism of action is not well understood. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00484-18
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http://dx.doi.org/10.1128/MCB.00484-18DOI Listing
January 2019
5 Reads

Phosphorylation of TIP60 suppresses 53BP1 localization at DNA damage sites.

Mol Cell Biol 2018 Oct 8. Epub 2018 Oct 8.

Department of Cancer Biology, Basser Center for BRCA, Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19146

Proper balance between the repair of DNA double-strand breaks (DSBs) by homologous recombination and nonhomologous end-joining is critical for maintaining genome integrity and preventing tumorigenesis. This balance is regulated and fine-tuned by a variety of factors, including cell cycle and the chromatin environment. The histone acetyltransferase TIP60 was previously shown to suppress pathologic end-joining and promote homologous recombination. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00209-18
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http://dx.doi.org/10.1128/MCB.00209-18DOI Listing
October 2018
1 Read
4.777 Impact Factor

Hsp70 Interacts with Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 To Regulate p38MAPK Stability and Myoblast Differentiation during Skeletal Muscle Regeneration.

Mol Cell Biol 2018 Dec 28;38(24). Epub 2018 Nov 28.

Department of Biochemistry and Molecular Biology, Zhejiang University School of Medicine, Hangzhou, China

The regenerative process of injured muscle is dependent on the fusion and differentiation of myoblasts derived from muscle stem cells. Hsp70 is important for maintaining skeletal muscle homeostasis and regeneration, but the precise cellular mechanism remains elusive. In this study, we found that Hsp70 was upregulated during myoblast differentiation. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00211-18
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http://dx.doi.org/10.1128/MCB.00211-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275188PMC
December 2018
4 Reads

Mediator Is Essential for Small Nuclear and Nucleolar RNA Transcription in Yeast.

Mol Cell Biol 2018 Dec 28;38(24). Epub 2018 Nov 28.

Department of Biology, Indiana University, Bloomington, Indiana, USA

Eukaryotic RNA polymerase II (RNAPII) transcribes mRNA genes and non-protein-coding RNA (ncRNA) genes, including those encoding small nuclear and nucleolar RNAs (sn/snoRNAs). In metazoans, RNAPII transcription of sn/snoRNAs is facilitated by a number of specialized complexes, but no such complexes have been discovered in yeast. It has been proposed that yeast sn/snoRNA and mRNA expression relies on a set of common factors, but the extent to which regulators of mRNA genes function at yeast sn/snoRNA genes is unclear. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00296-18
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http://dx.doi.org/10.1128/MCB.00296-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275182PMC
December 2018
5 Reads

New Player in Endosomal Trafficking: Differential Roles of Smad Anchor for Receptor Activation (SARA) Protein.

Mol Cell Biol 2018 Dec 28;38(24). Epub 2018 Nov 28.

Universidad Nacional de Córdoba (UNC), Ciudad Universitaria, Córdoba, Argentina

The development and maintenance of multicellular organisms require specialized coordination between external cellular signals and the proteins receiving stimuli and regulating responses. A critical role in the proper functioning of these processes is played by endosomal trafficking, which enables the transport of proteins to targeted sites as well as their return to the plasma membrane through its essential components, the endosomes. During this trafficking, signaling pathways controlling functions related to the endosomal system are activated both directly and indirectly. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00446-18
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http://dx.doi.org/10.1128/MCB.00446-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275186PMC
December 2018
1 Read

Expression of the Alternative Oxidase Influences Jun N-Terminal Kinase Signaling and Cell Migration.

Mol Cell Biol 2018 Dec 28;38(24). Epub 2018 Nov 28.

Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland

Downregulation of Jun N-terminal kinase (JNK) signaling inhibits cell migration in diverse model systems. In pupal development, attenuated JNK signaling in the thoracic dorsal epithelium leads to defective midline closure, resulting in cleft thorax. Here we report that concomitant expression of the alternative oxidase (AOX) was able to compensate for JNK pathway downregulation, substantially correcting the cleft thorax phenotype. Read More

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http://dx.doi.org/10.1128/MCB.00110-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275184PMC
December 2018
1 Read

Induction of hepatic metabolic functions by a novel variant of hepatocyte nuclear factor 4γ.

Mol Cell Biol 2018 Sep 17. Epub 2018 Sep 17.

Division of Molecular Science, Graduate School of Science and Technology, Gunma University, Kiryu, Gunma 376-8515, Japan

Hepatocyte nuclear factor 4α (HNF4α) is a critical factor for hepatocyte differentiation. HNF4α expression is decreased in hepatocellular carcinoma (HCC), which suggests a role in repression of hepatocyte dedifferentiation. In the present study, hepatic expression of HNF4γ was increased in liver-specific -null mice. Read More

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http://dx.doi.org/10.1128/MCB.00213-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275183PMC
September 2018
5 Reads

Human DnaJB6 Antiamyloid Chaperone Protects Yeast from Polyglutamine Toxicity Separately from Spatial Segregation of Aggregates.

Mol Cell Biol 2018 Dec 13;38(23). Epub 2018 Nov 13.

Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA

Polyglutamine (polyQ) aggregates are associated with pathology in protein-folding diseases and with toxicity in the yeast Protection from polyQ toxicity in yeast by human DnaJB6 coincides with sequestration of aggregates. Gathering of misfolded proteins into deposition sites by protein quality control (PQC) factors has led to the view that PQC processes protect cells by spatially segregating toxic aggregates. Whether DnaJB6 depends on this machinery to sequester polyQ aggregates, if this sequestration is needed for DnaJB6 to protect cells, and the identity of the deposition site are unknown. Read More

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http://dx.doi.org/10.1128/MCB.00437-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234286PMC
December 2018

Deficiency of the Endocytic Protein Hip1 Leads to Decreased Expression, Low Phosphocholine, and Kypholordosis.

Mol Cell Biol 2018 Dec 13;38(23). Epub 2018 Nov 13.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA

Deficiency of huntingtin-interacting protein 1 (Hip1) results in degenerative phenotypes. Here we generated a deficiency allele where a floxed transcriptional stop cassette and a human cDNA were knocked into intron 1 of the mouse locus. -mediated germ line excision of the stop cassette resulted in expression of HIP1 and rescue of the knockout phenotype. Read More

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http://dx.doi.org/10.1128/MCB.00385-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234285PMC
December 2018

APOBEC3H Subcellular Localization Determinants Define Zipcode for Targeting HIV-1 for Restriction.

Mol Cell Biol 2018 Dec 13;38(23). Epub 2018 Nov 13.

Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USA

APOBEC enzymes are DNA cytosine deaminases that normally serve as virus restriction factors, but several members, including APOBEC3H, also contribute to cancer mutagenesis. Despite their importance in multiple fields, little is known about cellular processes that regulate these DNA mutating enzymes. We show that APOBEC3H exists in two distinct subcellular compartments, cytoplasm and nucleolus, and that the structural determinants for each mechanism are genetically separable. Read More

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http://dx.doi.org/10.1128/MCB.00356-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234287PMC
December 2018
9 Reads

Native and Polyubiquitinated Forms of Dihydroceramide Desaturase Are Differentially Linked to Human Embryonic Kidney Cell Survival.

Mol Cell Biol 2018 Dec 13;38(23). Epub 2018 Nov 13.

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland, United Kingdom

There is controversy concerning the role of dihydroceramide desaturase (Degs1) in regulating cell survival, with studies showing that it can both promote and protect against apoptosis. We have therefore investigated the molecular basis for these opposing roles of Degs1. Treatment of HEK293T cells with the sphingosine kinase inhibitor SKi [2-(-hydroxyanilino)-4-(-chlorophenyl)thiazole] or fenretinide, but not the Degs1 inhibitor GT11 {-[(1,2)-2-hydroxy-1-hydroxymethyl-2-(2-tridecyl-1-cyclopropenyl)ethyl]octan-amide}, induced the polyubiquitination of Degs1 ( = 40 to 140 kDa) via a mechanism involving oxidative stress, p38 mitogen-activated protein kinase (MAPK), and Mdm2 (E3 ligase). Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00222-18
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http://dx.doi.org/10.1128/MCB.00222-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234290PMC
December 2018
3 Reads

RACK1 Specifically Regulates Translation through its Binding to Ribosomes.

Mol Cell Biol 2018 Sep 10. Epub 2018 Sep 10.

Molecular Histology and Cell Growth Unit, National Institute of Molecular Genetics "Romeo e Enrica Invernizzi" - INGM, via Francesco Sforza 35, 20122, Milan, Italy

The translational capability of ribosomes deprived of specific non-fundamental ribosomal proteins may be altered. Physiological mechanisms are scanty and it is unclear whether free ribosomal proteins can crosstalk with the signaling machinery. RACK1 (Receptor for Activated C Kinase 1) is a highly conserved scaffold protein, located on the 40S subunit near the mRNA exit channel. Read More

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http://dx.doi.org/10.1128/MCB.00230-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234289PMC
September 2018
2 Reads

The Cellular Senescence-Inhibited Gene Is Essential for PPM1A Myristoylation To Modulate Transforming Growth Factor β Signaling.

Mol Cell Biol 2018 Dec 13;38(23). Epub 2018 Nov 13.

Research Center on Aging, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Beijing, People's Republic of China

The cellular senescence-inhibited gene (CSIG) is implicated in important biological processes, including cellular senescence and apoptosis. Our work showed that CSIG is involved in the myristoylation of the serine/threonine protein phosphatase PPM1A. Previous research has shown that myristoylation is necessary for PPM1A to dephosphorylate Smad2 and Smad3. Read More

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http://dx.doi.org/10.1128/MCB.00414-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234292PMC
December 2018

Adaptation to Endoplasmic Reticulum Stress Requires Trans-phosphorylation within the Activation Loop of Protein Kinases Kin1 and Kin2, Orthologs of Human Microtubule Affinity-regulating Kinase.

Mol Cell Biol 2018 Sep 10. Epub 2018 Sep 10.

Department of Biological Sciences, UW-Milwaukee, Milwaukee, USA

Perturbations in endoplasmic reticulum (ER) homeostasis, a condition termed the "ER stress", activate the unfolded protein response (UPR), an intracellular network of signaling pathways. Recently, we have shown that protein kinase Kin1 and its paralog Kin2 in the budding yeast (orthologs of microtubule affinity-regulating kinase in humans) contribute to the UPR function. These Kin kinases contain a conserved kinase domain and an auto-inhibitory kinase-associated 1 (KA1) domain separated by a long undefined domain. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00266-18
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http://dx.doi.org/10.1128/MCB.00266-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234288PMC
September 2018
1 Read

Regulation of Transcription Factor SP1 by the β-Catenin Destruction Complex Modulates Wnt Response.

Mol Cell Biol 2018 Nov 29;38(22). Epub 2018 Oct 29.

Indian Institute of Science Education and Research, Pune, India

The ubiquitous transcription factor specificity protein 1 (SP1) is heavily modified posttranslationally. These modifications are critical for switching its functions and modulation of its transcriptional activity and DNA binding and stability. However, the mechanism governing the stability of SP1 by cellular signaling pathways is not well understood. Read More

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http://dx.doi.org/10.1128/MCB.00188-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206460PMC
November 2018
5 Reads

Myc-Associated Zinc Finger Protein Regulates the Proinflammatory Response in Colitis and Colon Cancer via STAT3 Signaling.

Mol Cell Biol 2018 Nov 29;38(22). Epub 2018 Oct 29.

Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, USA

Myc-associated zinc finger (MAZ) is a transcription factor highly upregulated in chronic inflammatory disease and several human cancers. In the present study, we found that MAZ protein is highly expressed in human ulcerative colitis and colon cancer. However, the precise role for MAZ in the progression of colitis and colon cancer is not well defined. Read More

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http://dx.doi.org/10.1128/MCB.00386-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206459PMC
November 2018
1 Read

Protein Phosphatase 1α and Cofilin Regulate Nuclear Translocation of NF-κB and Promote Expression of the Anti-Inflammatory Cytokine Interleukin-10 by T Cells.

Mol Cell Biol 2018 Nov 29;38(22). Epub 2018 Oct 29.

Institute of Immunology, Ruprecht Karls University, Heidelberg, Germany.

While several protein serine/threonine kinases control cytokine production by T cells, the roles of serine/threonine phosphatases are largely unexplored. Here, we analyzed the involvement of protein phosphatase 1α (PP1α) in cytokine synthesis following costimulation of primary human T cells. Small interfering RNA (siRNA)-mediated knockdown of PP1α (PP1) or expression of a dominant negative PP1α (D95N-PP1) drastically diminished interleukin-10 (IL-10) production. Read More

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http://dx.doi.org/10.1128/MCB.00041-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206454PMC
November 2018
1 Read

Fra-2 Expression in Osteoblasts Regulates Systemic Inflammation and Lung Injury through Osteopontin.

Mol Cell Biol 2018 Nov 29;38(22). Epub 2018 Oct 29.

Friedrich-Alexander University Erlangen-Nürnberg, Department of Internal Medicine 3 Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany

Inflammatory responses require mobilization of innate immune cells from the bone marrow. The functionality of this process depends on the state of the bone marrow microenvironment. We therefore hypothesized that molecular changes in osteoblasts, which are essential stromal cells of the bone marrow microenvironment, influence the inflammatory response. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00022-18
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http://dx.doi.org/10.1128/MCB.00022-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206458PMC
November 2018
6 Reads

The Gene, Implicated in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia, Encodes a Protein That Functions in Control of Endothelin and Glutamate Signaling.

Mol Cell Biol 2018 Nov 29;38(22). Epub 2018 Oct 29.

Department of Biological Sciences, Columbia University, New York, New York, USA

A GGGGCC repeat expansion in the () gene is the most common known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Several mechanisms have been proposed to account for its toxicity, including the possibility that reduced C9 protein levels contribute to disease. To investigate this possibility, we examined the effects of reduced C9 levels in several cell systems. Read More

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http://dx.doi.org/10.1128/MCB.00155-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206455PMC
November 2018
1 Read

So Many Roads: the Multifaceted Regulation of Autophagy Induction.

Mol Cell Biol 2018 Nov 15;38(21). Epub 2018 Oct 15.

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA

Autophagy is an evolutionary conserved, degradative process from single-cell eukaryotes, such as , to higher mammals, such as humans. The regulation of autophagy has been elucidated through the combined study of yeast, , mice, , and humans. MTOR, the major negative regulator of autophagy, and activating nutrient kinases, such as 5'-AMP-activated protein kinase (AMPK), interact with the autophagy regulatory complex: ULK1/2, RB1CC1, ATG13, and ATG101. Read More

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http://dx.doi.org/10.1128/MCB.00303-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189458PMC
November 2018
1 Read

p62-dependent phase separation of patient-derived KEAP1 mutations and NRF2.

Mol Cell Biol 2018 Aug 20. Epub 2018 Aug 20.

Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States.

Cancer-derived loss-of-function mutations in the KEAP1 tumor suppressor gene stabilize the NRF2 transcription factor, resulting in a pro-survival gene expression program that alters cellular metabolism and neutralizes oxidative stress. In a recent genotype-phenotype study, we classified 40% of KEAP1 mutations as ANCHOR mutants. By immunoprecipitation, these mutants bind more NRF2 than wild-type KEAP1 and ubiquitylate NRF2, but are incapable of promoting NRF2 degradation. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00644-17
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http://dx.doi.org/10.1128/MCB.00644-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206457PMC
August 2018
9 Reads

Transient Overexpression of VEGF-A in Adipose Tissue Promotes Energy Expenditure via Activation of the Sympathetic Nervous System.

Mol Cell Biol 2018 Aug 20. Epub 2018 Aug 20.

Center for Metabolic and Degenerative Diseases, the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, USA

Adipose-derived VEGF-A stimulates functional blood vessel formation in obese fat pads which in turn facilitates healthy expansion of the adipose tissue. However, the detailed mechanism(s) governing the process remains largely unknown. Here, we investigated the role of sympathetic nervous system activation in the process. Read More

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http://dx.doi.org/10.1128/MCB.00242-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206456PMC
August 2018
2 Reads
4.780 Impact Factor

A 3' Distal Otic Vesicle Enhancer Directs Inner Ear-Specific Expression.

Mol Cell Biol 2018 Nov 15;38(21). Epub 2018 Oct 15.

Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA

Transcription factor GATA3 plays vital roles in inner ear development, while regulatory mechanisms controlling its inner ear-specific expression are undefined. We demonstrate that a -regulatory element lying 571 kb 3' to the gene directs inner ear-specific expression, which we refer to as the otic vesicle enhancer (OVE). In transgenic murine embryos, a 1. Read More

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http://dx.doi.org/10.1128/MCB.00302-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189460PMC
November 2018
1 Read

Correction for Agudo-Ibáñez et al., "H-Ras Distribution and Signaling in Plasma Membrane Microdomains Are Regulated by Acylation and Deacylation Events".

Mol Cell Biol 2018 Sep 15;38(17). Epub 2018 Aug 15.

Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Cantabria, Departamento de Biología Molecular, Facultad de Medicina, Santander, Cantabria, Spain.

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http://dx.doi.org/10.1128/MCB.00335-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094049PMC
September 2018

E2F1 Mediates the Retinoic Acid-Induced Transcription of during Neuronal Differentiation in a Cell Division-Dependent Manner.

Mol Cell Biol 2018 Nov 15;38(21). Epub 2018 Oct 15.

Department of Biological Sciences, Seoul National University, Seoul, South Korea

The involvement of cell division in cellular differentiation has long been accepted. Cell division may be required not only for the expansion of a differentiated cell population but also for the execution of differentiation processes. Nonetheless, knowledge regarding how specific differentiation processes are controlled in a cell division-dependent manner is far from complete. Read More

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http://dx.doi.org/10.1128/MCB.00217-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189455PMC
November 2018

CD19 alterations emerging after CD19-directed immunotherapy cause retention of the misfolded protein in the endoplasmic reticulum.

Mol Cell Biol 2018 Aug 13. Epub 2018 Aug 13.

Divisions of Experimental Pathology and Oncology, and Protein & Proteomics Core Facility, Children's Hospital of Philadelphia

We have previously described a mechanism of acquired resistance of B-cell acute lymphoblastic leukemia to CD19-directed chimeric antigen receptor T-cell (CART) immunotherapy. It was based on in-frame insertions in or skipping of CD19 exon 2. To distinguish between epitope loss and defects in surface localization, we used retroviral transduction and genome editing to generate cell lines expressing CD19 exon 2 variants (CD19ex2vs) bearing VSV-G tags. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00383-18
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http://dx.doi.org/10.1128/MCB.00383-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189457PMC
August 2018
5 Reads

Decreased c-Myc mRNA Stability via the MicroRNA 141-3p/AUF1 Axis Is Crucial for p63α Inhibition of Cyclin D1 Gene Transcription and Bladder Cancer Cell Tumorigenicity.

Mol Cell Biol 2018 Nov 15;38(21). Epub 2018 Oct 15.

Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, USA

Bladder cancer (BC) ranks as the sixth most common cancer in the United States and is the leading cause of death in patients with urinary malignancies. p63 is a member of the p53 family and is believed to function as a tumor suppressor in human BCs. Our most recent studies revealed a previously unknown function of the RING of XIAP in promoting microRNA 4295 (miR-4295) transcription, thereby reducing p63α protein translation and enhancing normal urothelial transformation, whereas p63α upregulates hsp70 transcription, subsequently activating the HSP70/Wasf3/Wave3/matrix metalloproteinase 9 (MMP-9) axis and promoting BC cell invasion via initiating the transcription factor E2F1. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00273-18
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http://dx.doi.org/10.1128/MCB.00273-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189456PMC
November 2018
13 Reads

Growth Differentiation Factor 15 Maturation Requires Proteolytic Cleavage by PCSK3, -5, and -6.

Mol Cell Biol 2018 Nov 15;38(21). Epub 2018 Oct 15.

Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

Growth differentiation factor 15 (GDF15) is a secreted protein with pleotropic functions from the transforming growth factor β (TGF-β) family. GDF15 is synthesized as a precursor and undergoes proteolytic cleavage to generate mature GDF15. The strong appetite-suppressing effect of mature GDF15 makes it an attractive therapeutic agent/target for diseases such as obesity and cachexia. Read More

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http://mcb.asm.org/lookup/doi/10.1128/MCB.00249-18
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http://dx.doi.org/10.1128/MCB.00249-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6189459PMC
November 2018
12 Reads
4.780 Impact Factor