5,833 results match your criteria Cellular and molecular life sciences : CMLS[Journal]


Network mapping of the conformational heterogeneity of SOD1 by deploying statistical cluster analysis of FTIR spectra.

Cell Mol Life Sci 2019 Apr 22. Epub 2019 Apr 22.

Protein Folding and Dynamics Laboratory, Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, 700032, India.

A crucial contribution to the heterogeneity of the conformational landscape of a protein comes from the way an intermediate relates to another intermediate state in its journey from the unfolded to folded or misfolded form. Unfortunately, it is extremely hard to decode this relatedness in a quantifiable manner. Here, we developed an application of statistical cluster analyses to explore the conformational heterogeneity of a metalloenzyme, human cytosolic copper-zinc superoxide dismutase (SOD1), using the inputs from infrared spectroscopy. Read More

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http://dx.doi.org/10.1007/s00018-019-03108-2DOI Listing

NEAT1 regulates neuroglial cell mediating Aβ clearance via the epigenetic regulation of endocytosis-related genes expression.

Cell Mol Life Sci 2019 Apr 20. Epub 2019 Apr 20.

School of Life Sciences, Tsinghua University, Beijing, 100084, China.

The accumulation of intracellular β-amyloid peptide (Aβ) is important pathological characteristic of Alzheimer's disease (AD). However, the exact underlying molecular mechanism remains to be elucidated. Here, we reported that Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), a long n on-coding RNA, exhibits repressed expression in the early stage of AD and its down-regulation declines neuroglial cell mediating Aβ clearance via inhibiting expression of endocytosis-related genes. Read More

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http://dx.doi.org/10.1007/s00018-019-03074-9DOI Listing

Helicobacter pylori infection and gastrointestinal tract cancer biology: considering a double-edged sword reflection.

Cell Mol Life Sci 2019 Apr 20. Epub 2019 Apr 20.

Department of Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 8 Fanariou St, Byzantio, 551 33, Thessaloniki, Macedonia, Greece.

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http://dx.doi.org/10.1007/s00018-019-03106-4DOI Listing

Characterization of PPIB interaction in the P3H1 ternary complex and implications for its pathological mutations.

Cell Mol Life Sci 2019 Apr 16. Epub 2019 Apr 16.

Department of Pathophysiology, Shanghai Tongren Hospital/Faculty of Basic Medicine, Hongqiao International Institute of Medicine; Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

The P3H1/CRTAP/PPIB complex is essential for prolyl 3-hydroxylation and folding of procollagens in the endoplasmic reticulum (ER). Deficiency in any component of this ternary complex is associated with the misfolding of collagen and the onset of osteogenesis imperfecta. However, little structure information is available about how this ternary complex is assembled and retained in the ER. Read More

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http://dx.doi.org/10.1007/s00018-019-03102-8DOI Listing
April 2019
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Bcl-2 and IP compete for the ligand-binding domain of IPRs modulating Ca signaling output.

Cell Mol Life Sci 2019 Apr 16. Epub 2019 Apr 16.

Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine, Leuven Cancer Institute (LKI), KU Leuven, Campus Gasthuisberg O/N-1 Bus 802, Herestraat 49, 3000, Leuven, Belgium.

Bcl-2 proteins have emerged as critical regulators of intracellular Ca dynamics by directly targeting and inhibiting the IP receptor (IPR), a major intracellular Ca-release channel. Here, we demonstrate that such inhibition occurs under conditions of basal, but not high IPR activity, since overexpressed and purified Bcl-2 (or its BH4 domain) can inhibit IPR function provoked by low concentration of agonist or IP, while fails to attenuate against high concentration of agonist or IP. Surprisingly, Bcl-2 remained capable of inhibiting IPR1 channels lacking the residues encompassing the previously identified Bcl-2-binding site (a. Read More

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http://dx.doi.org/10.1007/s00018-019-03091-8DOI Listing
April 2019
1 Read

Computational algorithms for in silico profiling of activating mutations in cancer.

Cell Mol Life Sci 2019 Apr 13. Epub 2019 Apr 13.

Graduate Group in Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, PA, USA.

Methods to catalog and computationally assess the mutational landscape of proteins in human cancers are desirable. One approach is to adapt evolutionary or data-driven methods developed for predicting whether a single-nucleotide polymorphism (SNP) is deleterious to protein structure and function. In cases where understanding the mechanism of protein activation and regulation is desired, an alternative approach is to employ structure-based computational approaches to predict the effects of point mutations. Read More

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http://dx.doi.org/10.1007/s00018-019-03097-2DOI Listing
April 2019
1 Read

Protein tyrosine phosphatases: promising targets in pancreatic ductal adenocarcinoma.

Cell Mol Life Sci 2019 Apr 13. Epub 2019 Apr 13.

Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, Brazil.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. It is the fourth leading cause of cancer-related death and is associated with a very poor prognosis. KRAS driver mutations occur in approximately 95% of PDAC cases and cause the activation of several signaling pathways such as mitogen-activated protein kinase (MAPK) pathways. Read More

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http://dx.doi.org/10.1007/s00018-019-03095-4DOI Listing

Dysregulation of histone deacetylases in carcinogenesis and tumor progression: a possible link to apoptosis and autophagy.

Cell Mol Life Sci 2019 Apr 13. Epub 2019 Apr 13.

Cancer and Cell Death Laboratory, Department of Life Science, National Institute of Technology Rourkela, Rourkela, Odisha, 769008, India.

Dysregulation of the epigenome and constitutional epimutation lead to aberrant expression of the genes, which regulate cancer initiation and progression. Histone deacetylases (HDACs), which are highly conserved in yeast to humans, are known to regulate numerous proteins involved in the transcriptional regulation of chromatin structures, apoptosis, autophagy, and mitophagy. In addition, a non-permissive chromatin conformation is created by HDACs, preventing the transcription of the genes encoding the proteins associated with tumorigenesis. Read More

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http://dx.doi.org/10.1007/s00018-019-03098-1DOI Listing

The deubiquitinase OTUD5 regulates Ku80 stability and non-homologous end joining.

Cell Mol Life Sci 2019 Apr 12. Epub 2019 Apr 12.

Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, 38 Xueyuan Road, Beijing, 100191, China.

The ability of cells to repair DNA double-strand breaks (DSBs) is important for maintaining genome stability and eliminating oncogenic DNA lesions. Two distinct and complementary pathways, non-homologous end joining (NHEJ) and homologous recombination (HR), are employed by mammalian cells to repair DNA DSBs. Each pathway is tightly controlled in response to increased DSBs. Read More

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http://dx.doi.org/10.1007/s00018-019-03094-5DOI Listing

The role of the protein-RNA recognition code in neurodegeneration.

Authors:
Jozef Nahalka

Cell Mol Life Sci 2019 Apr 12. Epub 2019 Apr 12.

Institute of Chemistry, Centre for Glycomics, Slovak Academy of Sciences, Dubravska cesta 9, 84538, Bratislava, Slovak Republic.

MicroRNAs are small endogenous RNAs that pair and bind to sites on mRNAs to direct post-transcriptional repression. However, there is a possibility that microRNAs directly influence protein structure and activity, and this influence can be termed post-translational riboregulation. This conceptual review explores the literature on neurodegenerative disorders. Read More

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http://dx.doi.org/10.1007/s00018-019-03096-3DOI Listing
April 2019
3 Reads

Regulation of WNT5A and WNT11 during MSC in vitro chondrogenesis: WNT inhibition lowers BMP and hedgehog activity, and reduces hypertrophy.

Cell Mol Life Sci 2019 Apr 12. Epub 2019 Apr 12.

Research Center for Experimental Orthopaedics, Heidelberg University Hospital, Heidelberg, Germany.

Re-directing mesenchymal stromal cell (MSC) chondrogenesis towards a non-hypertrophic articular chondrocyte-(AC)-like phenotype is important for improving articular cartilage neogenesis to enhance clinical cartilage repair strategies. This study is the first to demonstrate that high levels of non-canonical WNT5A followed by WNT11 and LEF1 discriminated MSC chondrogenesis from AC re-differentiation. Moreover, β-catenin seemed incompletely silenced in differentiating MSCs, which altogether suggested a role for WNT signaling in hypertrophic MSC differentiation. Read More

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http://dx.doi.org/10.1007/s00018-019-03099-0DOI Listing

Chaperone-mediated autophagy degradation of IGF-1Rβ induced by NVP-AUY922 in pancreatic cancer.

Cell Mol Life Sci 2019 Apr 12. Epub 2019 Apr 12.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100050, China.

Enhancement of insulin-like growth factor 1 receptor (IGF-IR) degradation by heat shock protein 90 (HSP90) inhibitor is a potential antitumor therapeutic strategy. However, very little is known about how IGF-IR protein levels are degraded by HSP90 inhibitors in pancreatic cancer (PC). We found that the HSP90α inhibitor NVP-AUY922 (922) effectively downregulated and destabilized the IGF-1Rβ protein, substantially reduced the levels of downstream signaling molecules (p-AKT, AKT and p-ERK1/2), and resulted in growth inhibition and apoptosis in IGF-1Rβ-overexpressing PC cells. Read More

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http://dx.doi.org/10.1007/s00018-019-03080-xDOI Listing
April 2019
1 Read

Fbxo30 regulates chromosome segregation of oocyte meiosis.

Cell Mol Life Sci 2019 Apr 12. Epub 2019 Apr 12.

Center for Reproductive Medicine, Peking University Third Hospital, Beijing, 100191, China.

As the female gamete, meiotic oocytes provide not only half of the genome but also almost all stores for fertilization and early embryonic development. Because de novo mRNA transcription is absent in oocyte meiosis, protein-level regulations, especially the ubiquitin proteasome system, are more crucial. As the largest family of ubiquitin E3 ligases, Skp1-Cullin-F-box complexes recognize their substrates via F-box proteins with substrate-selected specificity. Read More

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http://link.springer.com/10.1007/s00018-019-03038-z
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http://dx.doi.org/10.1007/s00018-019-03038-zDOI Listing
April 2019
3 Reads

The roles and mechanisms of Leydig cells and myoid cells in regulating spermatogenesis.

Cell Mol Life Sci 2019 Apr 12. Epub 2019 Apr 12.

Hunan Normal University School of Medicine, 371 Tongzipo Road, Changsha, 410013, Hunan, China.

Spermatogenesis is fundamental to the establishment and maintenance of male reproduction, whereas its abnormality results in male infertility. Somatic cells, including Leydig cells, myoid cells, and Sertoli cells, constitute the microenvironment or the niche of testis, which is essential for regulating normal spermatogenesis. Leydig cells are an important component of the testicular stroma, while peritubular myoid cells are one of the major cell types of seminiferous tubules. Read More

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http://dx.doi.org/10.1007/s00018-019-03101-9DOI Listing

Mechanisms of neurodegeneration in a preclinical autosomal dominant retinitis pigmentosa knock-in model with a Rho mutation.

Cell Mol Life Sci 2019 Apr 11. Epub 2019 Apr 11.

Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Departments of Ophthalmology, Pathology, and Cell Biology, Columbia University, New York, NY, 10032, USA.

D190N, a missense mutation in rhodopsin, causes photoreceptor degeneration in patients with autosomal dominant retinitis pigmentosa (adRP). Two competing hypotheses have been developed to explain why D190N rod photoreceptors degenerate: (a) defective rhodopsin trafficking prevents proteins from correctly exiting the endoplasmic reticulum, leading to their accumulation, with deleterious effects or (b) elevated mutant rhodopsin expression and unabated signaling causes excitotoxicity. A knock-in D190N mouse model was engineered to delineate the mechanism of pathogenesis. Read More

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http://dx.doi.org/10.1007/s00018-019-03090-9DOI Listing

Adult stem cells at work: regenerating skeletal muscle.

Cell Mol Life Sci 2019 Apr 11. Epub 2019 Apr 11.

Leibniz Institute on Aging, Fritz Lipmann Institute, Beutenbergstrasse 11, 07745, Jena, Germany.

Skeletal muscle regeneration is a finely tuned process involving the activation of various cellular and molecular processes. Satellite cells, the stem cells of skeletal muscle, are indispensable for skeletal muscle regeneration. Their functionality is critically modulated by intrinsic signaling pathways as well as by interactions with the stem cell niche. Read More

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http://link.springer.com/10.1007/s00018-019-03093-6
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http://dx.doi.org/10.1007/s00018-019-03093-6DOI Listing
April 2019
2 Reads

Palmitic acid is an intracellular signaling molecule involved in disease development.

Cell Mol Life Sci 2019 Apr 9. Epub 2019 Apr 9.

School of Chinese Medicine, Centre of Clinical Research for Chinese Medicine, and Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Hong Kong, China.

Emerging evidence shows that palmitic acid (PA), a common fatty acid in the human diet, serves as a signaling molecule regulating the progression and development of many diseases at the molecular level. In this review, we focus on its regulatory roles in the development of five pathological conditions, namely, metabolic syndrome, cardiovascular diseases, cancer, neurodegenerative diseases, and inflammation. We summarize the clinical and epidemiological studies; and also the mechanistic studies which have identified the molecular targets for PA in these pathological conditions. Read More

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http://dx.doi.org/10.1007/s00018-019-03092-7DOI Listing
April 2019
5.808 Impact Factor

ATAT1 regulates forebrain development and stress-induced tubulin hyperacetylation.

Cell Mol Life Sci 2019 Apr 5. Epub 2019 Apr 5.

The Rosalind and Morris Goodman Cancer Research Center, McGill University, 1160 Pine Avenue West, Montreal, QC, H3A 1A3, Canada.

α-Tubulin acetyltransferase 1 (ATAT1) catalyzes acetylation of α-tubulin at lysine 40 in various organisms ranging from Tetrahymena to humans. Despite the importance in mammals suggested by studies of cultured cells, the mouse Atat1 gene is non-essential for survival, raising an intriguing question about its real functions in vivo. To address this question, we systematically analyzed a mouse strain lacking the gene. Read More

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http://link.springer.com/10.1007/s00018-019-03088-3
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http://dx.doi.org/10.1007/s00018-019-03088-3DOI Listing
April 2019
5 Reads

The expression of circulating miR-504 in plasma is associated with EGFR mutation status in non-small-cell lung carcinoma patients.

Cell Mol Life Sci 2019 Apr 5. Epub 2019 Apr 5.

Department of Genetics and Clinical Immunology, National Research Institute of Tuberculosis and Lung Diseases, 26 Plocka St., 01-138, Warsaw, Poland.

MicroRNAs (miRNAs), key regulators of gene expression at the post-transcriptional level, are grossly misregulated in some human cancers, including non-small-cell lung carcinoma (NSCLC). The aberrant expression of specific miRNAs results in the abnormal regulation of key components of signalling pathways in tumour cells. MiRNA levels and the activity of the gene targets, including oncogenes and tumour suppressors, produce feedback that changes miRNA expression levels and indicates the cell's genetic activity. Read More

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http://dx.doi.org/10.1007/s00018-019-03089-2DOI Listing
April 2019
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Plakophilin 1 but not plakophilin 3 regulates desmoglein clustering.

Cell Mol Life Sci 2019 Apr 4. Epub 2019 Apr 4.

Faculty of Medicine, Institute of Anatomy, Ludwig-Maximilians-Universität Munich, Pettenkoferstr. 11, 80336, Munich, Germany.

Plakophilins (Pkp) are desmosomal plaque proteins crucial for desmosomal adhesion and participate in the regulation of desmosomal turnover and signaling. However, direct evidence that Pkps regulate clustering and molecular binding properties of desmosomal cadherins is missing. Here, keratinocytes lacking either Pkp1 or 3 in comparison to wild type (wt) keratinocytes were characterized with regard to their desmoglein (Dsg) 1- and 3-binding properties and their capability to induce Dsg3 clustering. Read More

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http://dx.doi.org/10.1007/s00018-019-03083-8DOI Listing

Microglial activation in an amyotrophic lateral sclerosis-like model caused by Ranbp2 loss and nucleocytoplasmic transport impairment in retinal ganglion neurons.

Cell Mol Life Sci 2019 Apr 3. Epub 2019 Apr 3.

Department of Ophthalmology, Duke University Medical Center, DUEC 3802, 2351 Erwin Road, Durham, NC, 27710, USA.

Nucleocytoplasmic transport is dysregulated in sporadic and familial amyotrophic lateral sclerosis (ALS) and retinal ganglion neurons (RGNs) are purportedly involved in ALS. The Ran-binding protein 2 (Ranbp2) controls rate-limiting steps of nucleocytoplasmic transport. Mice with Ranbp2 loss in Thy1-motoneurons develop cardinal ALS-like motor traits, but the impairments in RGNs and the degree of dysfunctional consonance between RGNs and motoneurons caused by Ranbp2 loss are unknown. Read More

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http://dx.doi.org/10.1007/s00018-019-03078-5DOI Listing
April 2019
1 Read
5.808 Impact Factor

Role of mTORC1 in intestinal epithelial repair and tumorigenesis.

Cell Mol Life Sci 2019 Apr 3. Epub 2019 Apr 3.

Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA.

mTORC1 signaling is the prototypical pathway regulating protein synthesis and cell proliferation. mTORC1 is active in stem cells located at the base of intestinal crypts but silenced as transit-amplifying cells differentiate into enterocytes or secretory cells along the epithelium. After an insult or injury, self-limiting and controlled activation of mTORC1 is critical for the renewal and repair of intestinal epithelium. Read More

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http://dx.doi.org/10.1007/s00018-019-03085-6DOI Listing
April 2019
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AMPA receptors and their minions: auxiliary proteins in AMPA receptor trafficking.

Cell Mol Life Sci 2019 Apr 1. Epub 2019 Apr 1.

Institute of Cell Biology and Neuroscience and Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, Max-von-Laue-Str. 15, 60438, Frankfurt am Main, Germany.

To correctly transfer information, neuronal networks need to continuously adjust their synaptic strength to extrinsic stimuli. This ability, termed synaptic plasticity, is at the heart of their function and is, thus, tightly regulated. In glutamatergic neurons, synaptic strength is controlled by the number and function of AMPA receptors at the postsynapse, which mediate most of the fast excitatory transmission in the central nervous system. Read More

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http://dx.doi.org/10.1007/s00018-019-03068-7DOI Listing
April 2019
1 Read

The role of ASXL1 in hematopoiesis and myeloid malignancies.

Cell Mol Life Sci 2019 Mar 30. Epub 2019 Mar 30.

Division of Cellular Therapy, Advanced Clinical Research Center, and Division of Stem Cell Signaling, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 1088639, Japan.

Recent high-throughput genome-wide sequencing studies have identified recurrent somatic mutations in myeloid neoplasms. An epigenetic regulator, Additional sex combs-like 1 (ASXL1), is one of the most frequently mutated genes in all subtypes of myeloid malignancies. ASXL1 mutations are also frequently detected in clonal hematopoiesis, which is associated with an increased risk of mortality. Read More

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http://dx.doi.org/10.1007/s00018-019-03084-7DOI Listing
March 2019
2 Reads

Cdc14 activation requires coordinated Cdk1-dependent phosphorylation of Net1 and PP2A-Cdc55 at anaphase onset.

Cell Mol Life Sci 2019 Mar 29. Epub 2019 Mar 29.

Cell Cycle Group, Cancer Epigenetics and Biology Program (PEBC), Institut d'Investigacions Biomèdica de Bellvitge (IDIBELL), Av. Gran Via de L'Hospitalet 199-203, 08908, L'Hospitalet de Llobregat, Barcelona, Spain.

Exit from mitosis and completion of cytokinesis require the inactivation of mitotic cyclin-dependent kinase (Cdk) activity. In budding yeast, Cdc14 phosphatase is a key mitotic regulator that is activated in anaphase to counteract Cdk activity. In metaphase, Cdc14 is kept inactive in the nucleolus, where it is sequestered by its inhibitor, Net1. Read More

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http://dx.doi.org/10.1007/s00018-019-03086-5DOI Listing

Correction to: The coming-of-age of nucleocytoplasmic transport in motor neuron disease and neurodegeneration.

Authors:
Paulo A Ferreira

Cell Mol Life Sci 2019 Mar 28. Epub 2019 Mar 28.

Duke University Medical Center, DUEC 3802, 2351 Erwin Road, Durham, NC, 27710, USA.

The original version of this article unfortunately contained the following misspelling and formatting mistakes. Read More

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http://dx.doi.org/10.1007/s00018-019-03073-wDOI Listing

Using proteomics to identify ubiquitin ligase-substrate pairs: how novel methods may unveil therapeutic targets for neurodegenerative diseases.

Cell Mol Life Sci 2019 Mar 27. Epub 2019 Mar 27.

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, 2 Technology Place, Macquarie Park, Sydney, NSW, 2109, Australia.

Ubiquitin ligases play an integral role in fine-tuning signaling cascades necessary for normal cell function. Aberrant regulation of ubiquitin ligases has been implicated in several neurodegenerative diseases, generally, due to mutations within the E3 ligase itself. Several proteomic-based methods have recently emerged to facilitate the rapid identification of ligase-substrate pairs-a previously challenging feat due to the transient nature of ligase-substrate interactions. Read More

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http://dx.doi.org/10.1007/s00018-019-03082-9DOI Listing

Ascorbate inducible N259 glycans on prolyl 4-hydroxylase subunit α1 promote hydroxylation and secretion of type I collagen.

Cell Mol Life Sci 2019 Mar 27. Epub 2019 Mar 27.

State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, 44 Xiao Hong Shan Zhong Qu, Wuhan, 430071, Hubei, China.

Ascorbic acid (vitamin C, VC) increases the secretion of mature collagen by promoting the activity of prolyl 4-hydroxylase subunit α 1 (P4HA1). To explore the mechanism involved, we investigated the role of N-linked glycosylation, which can regulate enzyme activity. P4HA1 has two glycosylation sites, Asn (N) 113 and N259. Read More

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http://dx.doi.org/10.1007/s00018-019-03081-wDOI Listing

Genetics and the heart rate response to exercise.

Cell Mol Life Sci 2019 Mar 27. Epub 2019 Mar 27.

Department of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.

The acute heart rate response to exercise, i.e., heart rate increase during and heart rate recovery after exercise, has often been associated with all-cause and cardiovascular mortality. Read More

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http://dx.doi.org/10.1007/s00018-019-03079-4DOI Listing

Inter-kingdom signaling between gut microbiota and their host.

Cell Mol Life Sci 2019 Mar 25. Epub 2019 Mar 25.

Department of Gastroenterology, The Affiliated Hospital of North Sichuan Medical College, Road Wenhua 63#, Region Shunqing, Nanchong City, 637000, China.

The crosstalk between prokaryotic bacteria and eukaryotic gut epithelial cells has opened a new field for research. Quorum sensing system (QS) molecules employed by gut microbiota may play an essential role in host-microbial symbioses of the gut. Recent studies on the gut microbiome will unveil evolved mechanisms of the host to affect bacterial QS and shape bacterial composition. Read More

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http://dx.doi.org/10.1007/s00018-019-03076-7DOI Listing
March 2019
1 Read

Agonist-dependent development of delta opioid receptor tolerance in the colon.

Cell Mol Life Sci 2019 Mar 23. Epub 2019 Mar 23.

Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.

The use of opioid analgesics is severely limited due to the development of intractable constipation, mediated through activation of mu opioid receptors (MOR) expressed by enteric neurons. The related delta opioid receptor (DOR) is an emerging therapeutic target for chronic pain, depression and anxiety. Whether DOR agonists also promote sustained inhibition of colonic transit is unknown. Read More

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http://dx.doi.org/10.1007/s00018-019-03077-6DOI Listing
March 2019
2 Reads

The synaptic balance between sumoylation and desumoylation is maintained by the activation of metabotropic mGlu5 receptors.

Cell Mol Life Sci 2019 Mar 23. Epub 2019 Mar 23.

Université Côte d'Azur, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275, 660 route des lucioles, 06560, Valbonne, France.

Sumoylation is a reversible post-translational modification essential to the modulation of neuronal function, including neurotransmitter release and synaptic plasticity. A tightly regulated equilibrium between the sumoylation and desumoylation processes is critical to the brain function and its disruption has been associated with several neurological disorders. This sumoylation/desumoylation balance is governed by the activity of the sole SUMO-conjugating enzyme Ubc9 and a group of desumoylases called SENPs, respectively. Read More

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http://dx.doi.org/10.1007/s00018-019-03075-8DOI Listing

Stabilization of E2-EPF UCP protein is implicated in hepatitis B virus-associated hepatocellular carcinoma progression.

Cell Mol Life Sci 2019 Mar 22. Epub 2019 Mar 22.

Gene Therapy Research Unit, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.

Hepatitis B virus (HBV) X protein (HBx) is associated with hepatocarcinogenesis. E2-EPF ubiquitin carrier protein (UCP) catalyzes ubiquitination of itself and von Hippel-Lindau protein (pVHL) for degradation and associates with tumor growth and metastasis. However, it remains unknown whether HBx modulates the enzyme activity of UCP and thereby influences hepatocarcinogenesis. Read More

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http://dx.doi.org/10.1007/s00018-019-03066-9DOI Listing

E2F1 mediates the downregulation of POLD1 in replicative senescence.

Cell Mol Life Sci 2019 Mar 20. Epub 2019 Mar 20.

Clinical Laboratory of Xuanwu Hospital, Capital Medical University, Beijing, 100053, People's Republic of China.

POLD1, the catalytic subunit of DNA Pol δ, plays an important role in DNA synthesis and DNA damage repair, and POLD1 is downregulated in replicative senescence and mediates cell aging. However, the mechanisms of age-related downregulation of POLD1 expression have not been elucidated. In this study, four potential CpG islands in the POLD1 promoter were found, and the methylation levels of the POLD1 promoter were increased in aging 2BS cells, WI-38 cells and peripheral blood lymphocytes, especially at a single site, CpG 36, in CpG island 3. Read More

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http://dx.doi.org/10.1007/s00018-019-03070-zDOI Listing
March 2019
3 Reads
5.808 Impact Factor

A role for polycystin-1 and polycystin-2 in neural progenitor cell differentiation.

Cell Mol Life Sci 2019 Mar 20. Epub 2019 Mar 20.

Institute of Molecular and Cellular Anatomy, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.

Polycystin-1 (PC1) and polycystin-2 (PC2) are transmembrane proteins encoded by the Pkd1 and Pkd2 genes, respectively. Mutations in these genes are causative for the development of autosomal-dominant polycystic kidney disease. A prominent feature of this disease is an unbalanced cell proliferation. Read More

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http://dx.doi.org/10.1007/s00018-019-03072-xDOI Listing
March 2019
1 Read

Extracellular vesicle isolation methods: rising impact of size-exclusion chromatography.

Cell Mol Life Sci 2019 Mar 19. Epub 2019 Mar 19.

REMAR-IVECAT Group, Germans Trias i Pujol Health Science Research Institute, Can Ruti Campus, Badalona, Spain.

Extracellular vesicles (EVs) include a variety of nanosized vesicles released to the extracellular microenvironment by the vast majority of cells transferring bioactive lipids, proteins, mRNA, miRNA or non-coding RNA, as means of intercellular communication. Remarkably, among other fields of research, their use has become promising for immunomodulation, tissue repair and as source for novel disease-specific molecular signatures or biomarkers. However, a major challenge is to define accurate, reliable and easily implemented techniques for EV isolation due to their nanoscale size and high heterogeneity. Read More

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http://dx.doi.org/10.1007/s00018-019-03071-yDOI Listing
March 2019
1 Read

Mammalian haploid stem cells: establishment, engineering and applications.

Cell Mol Life Sci 2019 Mar 19. Epub 2019 Mar 19.

Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200120, China.

Haploid embryonic stem cells (haESCs) contain only one set of genomes inherited from the sperm or egg and are termed AG- or PG-haESCs, respectively. Mammalian haESCs show genome-wide hypomethylation and dysregulated imprinting, whereas they can sustain genome integrity during derivation and long-term propagation. In addition, haESCs exhibit similar pluripotency to traditional diploid ESCs but are unique because they function as gametes and have been used to produce semi-cloned animals. Read More

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http://dx.doi.org/10.1007/s00018-019-03069-6DOI Listing

LION: a simple and rapid method to achieve CRISPR gene editing.

Cell Mol Life Sci 2019 Mar 18. Epub 2019 Mar 18.

Lars Bolund Institute of Regenerative Medicine, BGI-Qingdao, BGI-Shenzhen, Qingdao, 266555, China.

The RNA-guided CRISPR-Cas9 technology has paved the way for rapid and cost-effective gene editing. However, there is still a great need for effective methods for rapid generation and validation of CRISPR/Cas9 gRNAs. Previously, we have demonstrated that highly efficient generation of multiplexed CRISPR guide RNA (gRNA) expression array can be achieved with Golden Gate Assembly (GGA). Read More

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http://dx.doi.org/10.1007/s00018-019-03064-xDOI Listing

A critical role for miR-142 in alveolar epithelial lineage formation in mouse lung development.

Cell Mol Life Sci 2019 Mar 18. Epub 2019 Mar 18.

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

The respiratory epithelium arises from alveolar epithelial progenitors which differentiate into alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. AT2 cells are stem cells in the lung critical for the repair process after injury. Mechanisms regulating AT1 and AT2 cell maturation are poorly defined. Read More

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http://dx.doi.org/10.1007/s00018-019-03067-8DOI Listing
March 2019
1 Read

Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia.

Cell Mol Life Sci 2019 Mar 18. Epub 2019 Mar 18.

Institute for Physiology and Pathophysiology, Johannes Kepler University Linz, Altenberger Strasse 69, 4040, Linz, Austria.

Medial vascular calcification has emerged as a putative key factor contributing to the excessive cardiovascular mortality of patients with chronic kidney disease (CKD). Hyperphosphatemia is considered a decisive determinant of vascular calcification in CKD. A critical role in initiation and progression of vascular calcification during elevated phosphate conditions is attributed to vascular smooth muscle cells (VSMCs), which are able to change their phenotype into osteo-/chondroblasts-like cells. Read More

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http://dx.doi.org/10.1007/s00018-019-03054-zDOI Listing
March 2019
3 Reads

Ciliary and cytoskeletal functions of an ancient monooxygenase essential for bioactive amidated peptide synthesis.

Cell Mol Life Sci 2019 Mar 16. Epub 2019 Mar 16.

Department of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT, 06030, USA.

Many secreted peptides used for cell-cell communication require conversion of a C-terminal glycine to an amide for bioactivity. This reaction is catalyzed only by the integral membrane protein peptidylglycine α-amidating monooxygenase (PAM). PAM has been highly conserved and is found throughout the metazoa; PAM-like sequences are also present in choanoflagellates, filastereans, unicellular and colonial chlorophyte green algae, dinoflagellates and haptophytes. Read More

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http://dx.doi.org/10.1007/s00018-019-03065-wDOI Listing

Long non-coding RNAs are emerging targets of phytochemicals for cancer and other chronic diseases.

Cell Mol Life Sci 2019 Mar 16. Epub 2019 Mar 16.

Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India.

The long non-coding RNAs (lncRNAs) are the crucial regulators of human chronic diseases. Therefore, approaches such as antisense oligonucleotides, RNAi technology, and small molecule inhibitors have been used for the therapeutic targeting of lncRNAs. During the last decade, phytochemicals and nutraceuticals have been explored for their potential against lncRNAs. Read More

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http://dx.doi.org/10.1007/s00018-019-03053-0DOI Listing

Neutrophil pyroptosis: new perspectives on sepsis.

Authors:
Lu Liu Bingwei Sun

Cell Mol Life Sci 2019 Mar 14. Epub 2019 Mar 14.

Department of Burns and Plastic Surgery, Affiliated Hospital, Jiangsu University, 438 Jiefang Rd., Zhenjiang, 212001, Jiangsu, China.

Pyroptosis is a caspase-1 or caspase-4/5/11-dependent programmed cell death associated with inflammation, which is initiated by inflammasomes or cytosolic LPS in innate immunity. Sepsis is a life-threatening organ dysfunction caused by an imbalance in the body's response to infection. It is a complex interaction between the pathogen and the host's immune system. Read More

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http://dx.doi.org/10.1007/s00018-019-03060-1DOI Listing

Cancer targeting peptides.

Cell Mol Life Sci 2019 Mar 15. Epub 2019 Mar 15.

Biology Program, New York University Abu Dhabi, PO Box 129188, Saadiyat Island Campus, Abu Dhabi, United Arab Emirates.

Despite continuing advances in the development of biomacromolecules for therapeutic purposes, successful application of these often large and hydrophilic molecules has been hindered by their inability to efficiently traverse the cellular plasma membrane. In recent years, cell-penetrating peptides (CPPs) have received considerable attention as a promising class of delivery vectors due to their ability to mediate the efficient import of a large number of cargoes in vitro and in vivo. However, the lack of target specificity of CPPs remains a major obstacle to their clinical development. Read More

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http://dx.doi.org/10.1007/s00018-019-03061-0DOI Listing
March 2019
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Proteins with calmodulin-like domains: structures and functional roles.

Cell Mol Life Sci 2019 Mar 15. Epub 2019 Mar 15.

Department of Biology, University of Copenhagen, 13 Universitetsparken, 2100, Copenhagen, Denmark.

The appearance of modular proteins is a widespread phenomenon during the evolution of proteins. The combinatorial arrangement of different functional and/or structural domains within a single polypeptide chain yields a wide variety of activities and regulatory properties to the modular proteins. In this review, we will discuss proteins, that in addition to their catalytic, transport, structure, localization or adaptor functions, also have segments resembling the helix-loop-helix EF-hand motifs found in Ca-binding proteins, such as calmodulin (CaM). Read More

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http://dx.doi.org/10.1007/s00018-019-03062-zDOI Listing
March 2019
2 Reads

To be or not to be: PP2A as a dual player in CNS functions, its role in neurodegeneration, and its interaction with brain insulin signaling.

Cell Mol Life Sci 2019 Mar 14. Epub 2019 Mar 14.

Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Accumulating evidence has reached the consensus that the balance of phosphorylation state of signaling molecules is a pivotal point in the regulation of cell signaling. Therefore, characterizing elements (kinases-phosphatases) in the phosphorylation balance are at great importance. However, the role of phosphatase enzymes is less investigated than kinase enzymes. Read More

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http://dx.doi.org/10.1007/s00018-019-03063-yDOI Listing
March 2019
3 Reads
5.808 Impact Factor

Phosphorylated and aggregated TDP-43 with seeding properties are induced upon mutant Huntingtin (mHtt) polyglutamine expression in human cellular models.

Cell Mol Life Sci 2019 Mar 12. Epub 2019 Mar 12.

Institut NeuroMyoGène, CNRS UMR5310, INSERM U1217, Faculté de Médecine Rockefeller, Université Claude Bernard Lyon I, 8 Avenue Rockefeller, 69373, Lyon Cedex 08, France.

The Tar DNA-Binding Protein 43 (TDP-43) and its phosphorylated isoform (pTDP-43) are the major components associated with ubiquitin positive/Tau-negative inclusions found in neurons and glial cells of patients suffering of amyotrophic lateral sclerosis (ALS) or frontotemporal lobar degeneration-TDP-43 (FTLD-TDP). Many studies have revealed that TDP-43 is also in the protein inclusions associated with neurodegenerative conditions other than ALS and FTLD-TDP, thus suggesting that this protein may be involved in the pathogenesis of a variety of neurological disorders. In brains of Huntington-affected patients, pTDP-43 aggregates were shown to co-localize with mutant Huntingtin (mHtt) inclusions. Read More

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http://link.springer.com/10.1007/s00018-019-03059-8
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http://dx.doi.org/10.1007/s00018-019-03059-8DOI Listing
March 2019
4 Reads

Disruption of mitochondrial dynamics affects behaviour and lifespan in Caenorhabditis elegans.

Cell Mol Life Sci 2019 Mar 6. Epub 2019 Mar 6.

Neuroscience Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC, 3800, Australia.

Mitochondria are essential components of eukaryotic cells, carrying out critical physiological processes that include energy production and calcium buffering. Consequently, mitochondrial dysfunction is associated with a range of human diseases. Fundamental to their function is the ability to transition through fission and fusion states, which is regulated by several GTPases. Read More

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http://dx.doi.org/10.1007/s00018-019-03024-5DOI Listing
March 2019
5.808 Impact Factor

Abnormalities in chemokine receptor recycling in chronic lymphocytic leukemia.

Cell Mol Life Sci 2019 Mar 4. Epub 2019 Mar 4.

Department of Life Sciences, University of Siena, Via Aldo Moro 2, 53100, Siena, Italy.

In addition to their modulation through de novo expression and degradation, surface levels of chemokine receptors are tuned by their ligand-dependent recycling to the plasma membrane, which ensures that engaged receptors become rapidly available for further rounds of signaling. Dysregulation of this process contributes to the pathogenesis of chronic lymphocytic leukemia (CLL) by enhancing surface expression of chemokine receptors, thereby favoring leukemic cell accumulation in the protective niche of lymphoid organs. In this review, we summarize our current understanding of the process of chemokine receptor recycling, focusing on the impact of its dysregulation in CLL. Read More

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http://dx.doi.org/10.1007/s00018-019-03058-9DOI Listing
March 2019
4 Reads

Enhanced cerebral branched-chain amino acid metabolism in R6/2 mouse model of Huntington's disease.

Cell Mol Life Sci 2019 Mar 4. Epub 2019 Mar 4.

Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark.

Huntington's disease (HD) is a hereditary and fatal disease causing profound neurodegeneration. Deficits in cerebral energy and neurotransmitter metabolism have been suggested to play a central role in the neuronal dysfunction and death associated with HD. The branched-chain amino acids (BCAAs), leucine, isoleucine and valine, are important for cerebral nitrogen homeostasis, neurotransmitter recycling and can be utilized as energy substrates in the tricarboxylic acid (TCA) cycle. Read More

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http://dx.doi.org/10.1007/s00018-019-03051-2DOI Listing