4,614 results match your criteria Cell death and differentiation[Journal]


Loss of Ryanodine Receptor 2 impairs neuronal activity-dependent remodeling of dendritic spines and triggers compensatory neuronal hyperexcitability.

Cell Death Differ 2020 Jul 8. Epub 2020 Jul 8.

German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Dendritic spines are postsynaptic domains that shape structural and functional properties of neurons. Upon neuronal activity, Ca transients trigger signaling cascades that determine the plastic remodeling of dendritic spines, which modulate learning and memory. Here, we study in mice the role of the intracellular Ca channel Ryanodine Receptor 2 (RyR2) in synaptic plasticity and memory formation. Read More

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http://dx.doi.org/10.1038/s41418-020-0584-2DOI Listing

Correction: MicroRNA-221 inhibits autophagy and promotes heart failure by modulating the p27/CDK2/mTOR axis.

Cell Death Differ 2020 Jul 6. Epub 2020 Jul 6.

The School and Hospital of Stomatology, Tianjin Medical University, 300070, Tianjin, PR China.

Since online publication of this article, the authors noticed that there were errors in the images used to compile Fig. 3c, 3g, and Supplementary Fig. 3g. Read More

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http://dx.doi.org/10.1038/s41418-020-0582-4DOI Listing

MCL-1 is essential for survival but dispensable for metabolic fitness of FOXP3 regulatory T cells.

Cell Death Differ 2020 Jul 1. Epub 2020 Jul 1.

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, Australia.

FOXP3 regulatory T (Treg) cells are essential for maintaining immunological tolerance. Given their importance in immune-related diseases, cancer and obesity, there is increasing interest in targeting the Treg cell compartment therapeutically. New pharmacological inhibitors that specifically target the prosurvival protein MCL-1 may provide this opportunity, as Treg cells are particularly reliant upon this protein. Read More

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http://dx.doi.org/10.1038/s41418-020-0585-1DOI Listing

LRIK interacts with the Ku70-Ku80 heterodimer enhancing the efficiency of NHEJ repair.

Cell Death Differ 2020 Jun 25. Epub 2020 Jun 25.

Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, PR China.

Despite recent advances in our understanding of the function of long noncoding RNAs (lncRNAs), their roles and functions in DNA repair pathways remain poorly understood. By screening a panel of uncharacterized lncRNAs to identify those whose transcription is induced by double-strand breaks (DSBs), we identified a novel lncRNA referred to as LRIK that interacts with Ku, which enhances the ability of the Ku heterodimer to detect the presence of DSBs. Here, we show that depletion of LRIK generates significantly enhanced sensitivity to DSB-inducing agents and reduced DSB repair efficiency. Read More

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http://dx.doi.org/10.1038/s41418-020-0581-5DOI Listing

The miR-92a-2-5p in exosomes from macrophages increases liver cancer cells invasion via altering the AR/PHLPP/p-AKT/β-catenin signaling.

Cell Death Differ 2020 Jun 25. Epub 2020 Jun 25.

George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology and The Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.

Early studies indicated that the androgen receptor (AR) might play important roles in the regulating of the initiation and progression of hepatocellular carcinoma (HCC), but its linkage to the surrounding macrophages and their impacts on the HCC progression remain unclear. Here we found that macrophages in liver cancer might function via altering the microRNA, miR-92a-2-5p, in exosomes to decrease liver cancer cells AR expression, which might then lead to increase the liver cancer cells invasion. Mechanism dissection revealed that miR-92a-2-5p from the exosomes could target the 3'UTR of AR mRNA to suppress AR translation, altering the PHLPP/p-AKT/β-catenin signaling to increase liver cancer cells invasion. Read More

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http://dx.doi.org/10.1038/s41418-020-0575-3DOI Listing

SIX1 cooperates with RUNX1 and SMAD4 in cell fate commitment of Müllerian duct epithelium.

Cell Death Differ 2020 Jun 22. Epub 2020 Jun 22.

Department of Cancer Biology and Genetics, The Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.

During female mammal reproductive tract development, epithelial cells of the lower Müllerian duct are committed to become stratified squamous epithelium of the vagina and ectocervix, when the expression of ΔNp63 transcription factor is induced by mesenchymal cells. The absence of ΔNp63 expression leads to adenosis, the putative precursor of vaginal adenocarcinoma. Our previous studies with genetically engineered mouse models have established that fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK), bone morphogenetic protein (BMP)/SMAD, and activin A/runt-related transcription factor 1 (RUNX1) signaling pathways are independently required for ΔNp63 expression in Müllerian duct epithelium (MDE). Read More

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http://dx.doi.org/10.1038/s41418-020-0579-zDOI Listing
June 2020
8.184 Impact Factor

Loss of RIPK3 does not impact MYC-driven lymphomagenesis or chemotherapeutic drug-induced killing of malignant lymphoma cells.

Cell Death Differ 2020 Jun 18. Epub 2020 Jun 18.

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.

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http://dx.doi.org/10.1038/s41418-020-0576-2DOI Listing

BRPF3-HUWE1-mediated regulation of MYST2 is required for differentiation and cell-cycle progression in embryonic stem cells.

Cell Death Differ 2020 Jun 18. Epub 2020 Jun 18.

Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.

Brpf-histone acetyltransferase (HAT) complexes have important roles in embryonic development and regulating differentiation in ESCs. Among Brpf family, Brpf3 is a scaffold protein of Myst2 histone acetyltransferase complex that plays crucial roles in gene regulation, DNA replication, development as well as maintaining pluripotency in embryonic stem cells (ESCs). However, its biological functions in ESCs are not elucidated. Read More

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http://dx.doi.org/10.1038/s41418-020-0577-1DOI Listing

Correction: Protein phosphatase 6 is a key factor regulating spermatogenesis.

Cell Death Differ 2020 Jun 18. Epub 2020 Jun 18.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper. Read More

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http://dx.doi.org/10.1038/s41418-020-0574-4DOI Listing

Yin Yang 1 is required for PHD finger protein 20-mediated myogenic differentiation in vitro and in vivo.

Cell Death Differ 2020 Jun 18. Epub 2020 Jun 18.

Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, 35015, South Korea.

The development of skeletal muscle requires progression of a highly ordered cascade of events comprising myogenic lineage commitment, myoblast proliferation, and terminal differentiation. The process of myogenesis is controlled by several myogenic transcription factors that act as terminal effectors of signaling cascades and produce appropriate developmental stage-specific transcripts. PHD finger protein 20 (PHF20) is a multidomain protein and subunit of a lysine acetyltransferase complex that acetylates histone H4 and p53, but its function is unclear. Read More

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http://dx.doi.org/10.1038/s41418-020-0580-6DOI Listing

An oncogenic viral interferon regulatory factor upregulates CUB domain-containing protein 1 to promote angiogenesis by hijacking transcription factor lymphoid enhancer-binding factor 1 and metastasis suppressor CD82.

Cell Death Differ 2020 Jun 17. Epub 2020 Jun 17.

Department of Microbiology, Nanjing Medical University, Nanjing, 211166, P.R. China.

Kaposi's sarcoma (KS), a highly angiogenic and invasive vascular tumor, is the most common AIDS-associated cancer caused by KS-associated herpesvirus (KSHV) infection. We have recently shown that KSHV-encoded viral interferon regulatory factor 1 (vIRF1) contributes to KSHV-induced cell motility (PLoS Pathog. 15:e1007578, 2019). Read More

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http://dx.doi.org/10.1038/s41418-020-0578-0DOI Listing
June 2020
8.184 Impact Factor

SUGT1 controls susceptibility to HIV-1 infection by stabilizing microtubule plus-ends.

Cell Death Differ 2020 Jun 8. Epub 2020 Jun 8.

Cell Death and Aging Team, Gustave Roussy Cancer Campus, F-94805, Villejuif, France.

Understanding the viral-host cell interface during HIV-1 infection is a prerequisite for the development of innovative antiviral therapies. Here we show that the suppressor of G2 allele of skp1 (SUGT1) is a permissive factor for human immunodeficiency virus (HIV)-1 infection. Expression of SUGT1 increases in infected cells on human brain sections and in permissive host cells. Read More

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http://dx.doi.org/10.1038/s41418-020-0573-5DOI Listing
June 2020
8.184 Impact Factor

Organoid systems to study the human female reproductive tract and pregnancy.

Cell Death Differ 2020 Jun 3. Epub 2020 Jun 3.

Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.

Both the proper functioning of the female reproductive tract (FRT) and normal placental development are essential for women's health, wellbeing, and pregnancy outcome. The study of the FRT in humans has been challenging due to limitations in the in vitro and in vivo tools available. Recent developments in 3D organoid technology that model the different regions of the FRT include organoids of the ovaries, fallopian tubes, endometrium and cervix, as well as placental trophoblast. Read More

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http://dx.doi.org/10.1038/s41418-020-0565-5DOI Listing

RBMX is required for activation of ATR on repetitive DNAs to maintain genome stability.

Cell Death Differ 2020 Jun 3. Epub 2020 Jun 3.

MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510006, China.

ATR is a master regulator of cell response to replication stress. Adequate activation of ATR is essential for preventing genome aberrance induced by replication defect. However, the mechanism underlying ATR activation is not fully understood. Read More

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http://dx.doi.org/10.1038/s41418-020-0570-8DOI Listing

USP22 positively modulates ERα action via its deubiquitinase activity in breast cancer.

Cell Death Differ 2020 Jun 3. Epub 2020 Jun 3.

Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, and Key laboratory of Medical Cell Biology, Ministry of Education, School of Life Sciences, China Medical University, Shenyang, 110122, Liaoning, China.

Estrogen receptor α (ERα) is the crucial factor in ERα-positive breast cancer progression. Endocrine therapies targeting ERα signaling is one of the widely used therapeutic strategies for breast cancer. However, a large number of the patients become refractory to therapy. Read More

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http://dx.doi.org/10.1038/s41418-020-0568-2DOI Listing

Brain organoids: an ensemble of bioassays to investigate human neurodevelopment and disease.

Cell Death Differ 2020 Jun 1. Epub 2020 Jun 1.

Institute of Molecular Biotechnology of Austrian academy of sciences (IMBA), Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, 1030, Vienna, Austria.

Understanding etiology of human neurological and psychiatric diseases is challenging. Genomic changes, protracted development, and histological features unique to human brain development limit the disease aspects that can be investigated using model organisms. Hence, in order to study phenotypes associated with human brain development, function, and disease, it is necessary to use alternative experimental systems that are accessible, ethically justified, and replicate human context. Read More

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http://dx.doi.org/10.1038/s41418-020-0566-4DOI Listing

Ubiquitin ligase CHIP regulates OTUD3 stability and suppresses tumour metastasis in lung cancer.

Cell Death Differ 2020 Jun 1. Epub 2020 Jun 1.

State Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, 100850, Beijing, China.

Ovarian tumour domain-containing protein 3 (OTUD3), a key OTU (ovarian tumour protease) family deubiquitylase, plays context-dependent roles in cancers. It suppresses tumorigenesis in breast, colon, liver and cervical cancer through stabilizing PTEN (phosphatase and tension homologue deleted on chromosome 10) while promotes lung tumorigenesis through stabilizing GRP78 (The glucose-regulated protein 78 kDa). The regulation especially post-translational modification of OTUD3 remains unclear. Read More

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http://dx.doi.org/10.1038/s41418-020-0571-7DOI Listing

Estrogen and estrogen receptors chauffeur the sex-biased autophagic action in liver.

Cell Death Differ 2020 Jun 1. Epub 2020 Jun 1.

South Ehime Fisheries Research Center, Ehime University, Ainan, 798-4206, Japan.

Autophagy, or cellular self-digestion, is an essential cellular process imperative for energy homeostasis, development, differentiation, and survival. However, the intrinsic factors that bring about the sex-biased differences in liver autophagy are still unknown. In this work, we found that autophagic genes variably expresses in the steroidogenic tissues, mostly abundant in liver, and is influenced by the individual's sexuality. Read More

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http://dx.doi.org/10.1038/s41418-020-0567-3DOI Listing

Olig2 SUMOylation protects against genotoxic damage response by antagonizing p53 gene targeting.

Cell Death Differ 2020 Jun 1. Epub 2020 Jun 1.

Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Posttranslational modifications of nuclear proteins, including transcription factors, nuclear receptors, and their coregulators, have attracted much attention in cancer research. Although phosphorylation of oligodendrocyte transcription factor 2 (Olig2) may contribute to the notorious resistance of gliomas to radiation and genotoxic drugs, the precise mechanisms remain elusive. We show here that in addition to phosphorylation, Olig2 is also conjugated by small ubiquitin-like modifier-1 (SUMO1) at three lysine residues K27, K76, and K112. Read More

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http://dx.doi.org/10.1038/s41418-020-0569-1DOI Listing

Dual functions of Rack1 in regulating Hedgehog pathway.

Cell Death Differ 2020 May 28. Epub 2020 May 28.

State Key Laboratory of Crop Biology, College of Life Sciences, Shandong Agricultural University, 271018, Tai'an, China.

Hedgehog (Hh) pathway plays multiple roles in many physiological processes and its dysregulation leads to congenital disorders and cancers. Hh regulates the cellular localization of Smoothened (Smo) and the stability of Cubitus interruptus (Ci) to fine-tune the signal outputs. However, the underlying mechanisms are still unclear. Read More

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http://dx.doi.org/10.1038/s41418-020-0563-7DOI Listing

Beclin 1 functions as a negative modulator of MLKL oligomerisation by integrating into the necrosome complex.

Cell Death Differ 2020 May 26. Epub 2020 May 26.

Department of Biochemistry, College of Life science and Biotechnology, Yonsei University, Seoul, Korea.

Necroptosis is a form of regulated cell death caused by formation of the necrosome complex. However, the factors modulating this process and the systemic pathophysiological effects of necroptosis are yet to be understood. Here, we identified that Beclin 1 functions as an anti-necroptosis factor by being recruited into the necrosome complex upon treatment with TNFα, Smac mimetic, and pan-caspase inhibitor and by repressing MLKL oligomerisation, thus preventing the disruption of the plasma membrane. Read More

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http://dx.doi.org/10.1038/s41418-020-0561-9DOI Listing

BH3 mimetics selectively eliminate chemotherapy-induced senescent cells and improve response in TP53 wild-type breast cancer.

Cell Death Differ 2020 May 26. Epub 2020 May 26.

Department of Biochemistry and Molecular Biology, Tulane Medical School, New Orleans, LA, USA.

TP53 wild-type breast tumors rarely undergo a complete pathological response after chemotherapy treatment. These patients have an extremely poor survival rate and studies show these tumors preferentially undergo senescence instead of apoptosis. These senescent cells persist after chemotherapy and secrete cytokines and chemokines comprising the senescence associated secretory phenotype, which promotes survival, proliferation, and metastasis. Read More

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http://dx.doi.org/10.1038/s41418-020-0564-6DOI Listing

Arginine hypomethylation-mediated proteasomal degradation of histone H4-an early biomarker of cellular senescence.

Cell Death Differ 2020 May 23. Epub 2020 May 23.

The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal University, Changchun, China.

Senescence is accompanied with histones level alteration; however, the roles and the mechanisms of histone reduction in cellular senescence are largely unknown. Protein arginine methyltransferase 1 (PRMT1) is the major enzyme that generates monomethyl and asymmetrical dimethyl arginine. Here we showed that abrogation of PRMT1-mediated senescence was accompanied with decreasing histone H4 level. Read More

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http://dx.doi.org/10.1038/s41418-020-0562-8DOI Listing

Stress-induced TRAILR2 expression overcomes TRAIL resistance in cancer cell spheroids.

Cell Death Differ 2020 May 20. Epub 2020 May 20.

Institute of Cell Biology and Immunology, University of Stuttgart, 70569, Stuttgart, Germany.

The influence of 3D microenvironments on apoptosis susceptibility remains poorly understood. Here, we studied the susceptibility of cancer cell spheroids, grown to the size of micrometastases, to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Interestingly, pronounced, spatially coordinated response heterogeneities manifest within spheroidal microenvironments: In spheroids grown from genetically identical cells, TRAIL-resistant subpopulations enclose, and protect TRAIL-hypersensitive cells, thereby increasing overall treatment resistance. Read More

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http://dx.doi.org/10.1038/s41418-020-0559-3DOI Listing
May 2020
8.184 Impact Factor

LOXL1 confers antiapoptosis and promotes gliomagenesis through stabilizing BAG2.

Cell Death Differ 2020 May 18. Epub 2020 May 18.

Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, 510006, China.

The lysyl oxidase (LOX) family is closely related to the progression of glioma. To ensure the clinical significance of LOX family in glioma, The Cancer Genome Atlas (TCGA) database was mined and the analysis indicated that higher LOXL1 expression was correlated with more malignant glioma progression. The functions of LOXL1 in promoting glioma cell survival and inhibiting apoptosis were studied by gain- and loss-of-function experiments in cells and animals. Read More

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http://dx.doi.org/10.1038/s41418-020-0558-4DOI Listing

FOXF2 deficiency accelerates the visceral metastasis of basal-like breast cancer by unrestrictedly increasing TGF-β and miR-182-5p.

Cell Death Differ 2020 May 18. Epub 2020 May 18.

Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin, 300060, China.

The mesenchymal transcription factor forkhead box F2 (FOXF2) is a critical regulator of embryogenesis and tissue homeostasis. Our previous studies demonstrated that FOXF2 is ectopically expressed in basal-like breast cancer (BLBC) cells and that FOXF2 deficiency promotes the epithelial-mesenchymal transition and aggressiveness of BLBC cells. In this study, we found that FOXF2 controls transforming growth factor-beta (TGF-β)/SMAD signaling pathway activation through transrepression of TGF-β-coding genes in BLBC cells. Read More

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http://dx.doi.org/10.1038/s41418-020-0555-7DOI Listing

Twist2 promotes CD8 T-cell differentiation by repressing ThPOK expression.

Cell Death Differ 2020 May 18. Epub 2020 May 18.

Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.

CD4/CD8 T-cell lineage differentiation is a key process in immune system development; however, a defined regulator(s) that converts the signal from T-cell receptor and co-receptor complexes into lineage differentiation remains unclear. Here, we show that Twist2 is a critical factor in CD4/CD8 thymocyte differentiation. Twist2 expression is differentially regulated by T-cell receptor signaling, leading to differentiation into the CD4 or CD8 lineage. Read More

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http://dx.doi.org/10.1038/s41418-020-0560-xDOI Listing

The proteasome activator REGγ accelerates cardiac hypertrophy by declining PP2Acα-SOD2 pathway.

Cell Death Differ 2020 May 18. Epub 2020 May 18.

Department of Cardiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.

Pathological cardiac hypertrophy eventually leads to heart failure without adequate treatment. REGγ is emerging as 11S proteasome activator of 20S proteasome to promote the degradation of cellular proteins in a ubiquitin- and ATP-independent manner. Here, we found that REGγ was significantly upregulated in the transverse aortic constriction (TAC)-induced hypertrophic hearts and angiotensin II (Ang II)-treated cardiomyocytes. Read More

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http://dx.doi.org/10.1038/s41418-020-0554-8DOI Listing

Staufen 1 amplifies proapoptotic activation of the unfolded protein response.

Cell Death Differ 2020 May 15. Epub 2020 May 15.

Department of Neurology, University of Utah, 175 North Medical Drive East, 5th Floor, Salt Lake City, UT, 84132, USA.

Staufen-1 (STAU1) is an RNA-binding protein that becomes highly overabundant in numerous neurodegenerative disease models, including those carrying mutations in presenilin1 (PSEN1), microtubule-associated protein tau (MAPT), huntingtin (HTT), TAR DNA-binding protein-43 gene (TARDBP), or C9orf72. We previously reported that elevations in STAU1 determine autophagy defects and its knockdown is protective in models of several neurodegenerative diseases. Additional functional consequences of STAU1 overabundance, however, have not been investigated. Read More

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http://dx.doi.org/10.1038/s41418-020-0553-9DOI Listing

Genome-scale screening of deubiquitinase subfamily identifies USP3 as a stabilizer of Cdc25A regulating cell cycle in cancer.

Cell Death Differ 2020 May 15. Epub 2020 May 15.

Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, Republic of Korea.

Conventional screening methods for deubiquitinating enzymes (DUBs) have important limitations. A loss-of-function study based on the knockout of DUB genes in mammalian cells can provide an excellent model for exploring DUB function. Here, we used CRISPR-Cas9 to perform genome-scale knockout of the entire set of genes encoding ubiquitin-specific proteases (USPs), a DUB subfamily, and then systematically screened for DUBs that stabilize the Cdc25A oncoprotein. Read More

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http://dx.doi.org/10.1038/s41418-020-0557-5DOI Listing
May 2020
8.184 Impact Factor

Uncovering the PIDDosome and caspase-2 as regulators of organogenesis and cellular differentiation.

Cell Death Differ 2020 Jul 15;27(7):2037-2047. Epub 2020 May 15.

Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.

The PIDDosome is a multiprotein complex that drives activation of caspase-2, an endopeptidase originally implicated in apoptosis. Yet, unlike other caspases involved in cell death and inflammation, caspase-2 seems to exert additional versatile functions unrelated to cell death. These emerging roles range from control of transcription factor activity to ploidy surveillance. Read More

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http://dx.doi.org/10.1038/s41418-020-0556-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308375PMC

Correction: Alpha synuclein aggregation drives ferroptosis: an interplay of iron, calcium and lipid peroxidation.

Cell Death Differ 2020 May 14. Epub 2020 May 14.

UCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK.

An amendment to this paper has been published and can be accessed via a link at the top of the paper. Read More

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http://dx.doi.org/10.1038/s41418-020-0552-xDOI Listing
May 2020
8.184 Impact Factor

Adipogenesis of skeletal muscle fibro/adipogenic progenitors is affected by the WNT5a/GSK3/β-catenin axis.

Cell Death Differ 2020 May 7. Epub 2020 May 7.

Department of Biology, University of Rome "Tor Vergata", 00133, Rome, Italy.

Fibro/Adipogenic Progenitors (FAPs) are muscle-interstitial progenitors mediating pro-myogenic signals that are critical for muscle homeostasis and regeneration. In myopathies, the autocrine/paracrine constraints controlling FAP adipogenesis are released causing fat infiltrates. Here, by combining pharmacological screening, high-dimensional mass cytometry and in silico network modeling with the integration of single-cell/bulk RNA sequencing data, we highlighted the canonical WNT/GSK/β-catenin signaling as a crucial pathway modulating FAP adipogenesis triggered by insulin signaling. Read More

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http://dx.doi.org/10.1038/s41418-020-0551-yDOI Listing

Monoglyceride lipase mediates tumor-suppressive effects by promoting degradation of X-linked inhibitor of apoptosis protein.

Cell Death Differ 2020 May 6. Epub 2020 May 6.

Department of Pharmacology, Upstate Medical University State University of New York, Syracuse, NY, 13210, USA.

We have previously reported that Monoglyceride Lipase (MGL) expression is absent or reduced in various human malignancies and MGL-deficient mice develop tumors in multiple organs. Evidence also suggests MGL to be a tumor suppressor, however, the mechanisms underlying its tumor-suppressive actions remain to be investigated. Here, we report a novel function of MGL as a negative regulator of XIAP, an important inhibitor of apoptosis. Read More

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http://dx.doi.org/10.1038/s41418-020-0549-5DOI Listing

Chemical activation of SAT1 corrects diet-induced metabolic syndrome.

Cell Death Differ 2020 May 6. Epub 2020 May 6.

Centre de Recherche des Cordeliers, INSERM U1138, Team "Metabolism, Cancer & Immunity", Sorbonne Université, Université de Paris, Paris, France.

The pharmacological targeting of polyamine metabolism is currently under the spotlight for its potential in the prevention and treatment of several age-associated disorders. Here, we report the finding that triethylenetetramine dihydrochloride (TETA), a copper-chelator agent that can be safely administered to patients for the long-term treatment of Wilson disease, exerts therapeutic benefits in animals challenged with hypercaloric dietary regimens. TETA reduced obesity induced by high-fat diet, excessive sucrose intake, or leptin deficiency, as it reduced glucose intolerance and hepatosteatosis, but induced autophagy. Read More

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http://dx.doi.org/10.1038/s41418-020-0550-zDOI Listing

Compensation between Wnt-driven tumorigenesis and cellular responses to ribosome biogenesis inhibition in the murine intestinal epithelium.

Cell Death Differ 2020 Apr 30. Epub 2020 Apr 30.

Early Mammalian Development and Stem Cell Biology, Institut Pasteur, CNRS UMR 3738, 25 rue du Dr. Roux, F-75015, Paris, France.

Ribosome biogenesis inhibition causes cell cycle arrest and apoptosis through the activation of tumor suppressor-dependent surveillance pathways. These responses are exacerbated in cancer cells, suggesting that targeting ribosome synthesis may be beneficial to patients. Here, we characterize the effect of the loss-of-function of Notchless (Nle), an essential actor of ribosome biogenesis, on the intestinal epithelium undergoing tumor initiation due to acute Apc loss-of-function. Read More

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http://dx.doi.org/10.1038/s41418-020-0548-6DOI Listing

Critical role of histone H3 lysine 27 demethylase Kdm6b in the homeostasis and function of medullary thymic epithelial cells.

Cell Death Differ 2020 Apr 28. Epub 2020 Apr 28.

Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, State Key Laboratory of Respiratory Disease, Guangzhou, 510000, China.

Medullary thymic epithelial cells (mTECs) play a central role in the establishment of T cell central immunological tolerance by promiscuously expressing tissue-restricted antigens (TRAs) and presenting them to developing T cells, leading to deletion of T cells responding to self-antigens. However, molecular mechanisms especially epigenetic regulation of mTEC homeostasis and TRA expression remain elusive. Here we show that the H3K27 demethylase Kdm6b is essential to maintain the postnatal thymic medulla by promoting mTEC survival and regulating the expression of TRA genes. Read More

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http://dx.doi.org/10.1038/s41418-020-0546-8DOI Listing

CD9 induces cellular senescence and aggravates atherosclerotic plaque formation.

Cell Death Differ 2020 Apr 28. Epub 2020 Apr 28.

Department of Biochemistry and Molecular Biology, Yeungnam University, Daegu, 42415, Republic of Korea.

CD9, a 24 kDa tetraspanin membrane protein, is known to regulate cell adhesion and migration, cancer progression and metastasis, immune and allergic responses, and viral infection. CD9 is upregulated in senescent endothelial cells, neointima hyperplasia, and atherosclerotic plaques. However, its role in cellular senescence and atherosclerosis remains undefined. Read More

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http://dx.doi.org/10.1038/s41418-020-0537-9DOI Listing

JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction.

Cell Death Differ 2020 Apr 28. Epub 2020 Apr 28.

Department of Biology, University of Rome Tor Vergata, Rome, Italy.

The Activation-Induced Cell Death (AICD) is a stimulation-dependent form of apoptosis used by the organism to shutdown T-cell response once the source of inflammation has been eliminated, while allowing the generation of immune memory. AICD is thought to progress through the activation of the extrinsic Fas/FasL pathway of cell death, leading to cytochrome-C release through caspase-8 and Bid activation. We recently described that, early upon AICD induction, mitochondria undergo structural alterations, which are required to promote cytochrome-C release and execute cell death. Read More

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http://dx.doi.org/10.1038/s41418-020-0540-1DOI Listing

R-spondin2 signaling is required for oocyte-driven intercellular communication and follicular growth.

Cell Death Differ 2020 Apr 27. Epub 2020 Apr 27.

Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.

R-spondin2 (RSPO2) is a member of the R-spondin family, which are secreted activators of the WNT/β-catenin (CTNNB1) signaling pathway. In the mouse postnatal ovary, WNT/CTNNB1 signaling is active in the oocyte and in the neighboring supporting cells, the granulosa cells. Although the role of Rspo2 has been previously studied using in vitro experiments, the results are conflicting and the in vivo ovarian function of Rspo2 remains unclear. Read More

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http://dx.doi.org/10.1038/s41418-020-0547-7DOI Listing

Alpha synuclein aggregation drives ferroptosis: an interplay of iron, calcium and lipid peroxidation.

Cell Death Differ 2020 Apr 27. Epub 2020 Apr 27.

UCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK.

Protein aggregation and abnormal lipid homeostasis are both implicated in neurodegeneration through unknown mechanisms. Here we demonstrate that aggregate-membrane interaction is critical to induce a form of cell death called ferroptosis. Importantly, the aggregate-membrane interaction that drives ferroptosis depends both on the conformational structure of the aggregate, as well as the oxidation state of the lipid membrane. Read More

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http://dx.doi.org/10.1038/s41418-020-0542-zDOI Listing
April 2020
8.184 Impact Factor

Targeting triple-negative breast cancers with the Smac-mimetic birinapant.

Cell Death Differ 2020 Apr 27. Epub 2020 Apr 27.

The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.

Smac mimetics target inhibitor of apoptosis (IAP) proteins, thereby suppressing their function to facilitate tumor cell death. Here we have evaluated the efficacy of the preclinical Smac-mimetic compound A and the clinical lead birinapant on breast cancer cells. Both exhibited potent in vitro activity in triple-negative breast cancer (TNBC) cells, including those from patient-derived xenograft (PDX) models. Read More

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http://dx.doi.org/10.1038/s41418-020-0541-0DOI Listing

Inhibition of the autophagic protein ULK1 attenuates axonal degeneration in vitro and in vivo, enhances translation, and modulates splicing.

Cell Death Differ 2020 Apr 27. Epub 2020 Apr 27.

Department of Neurology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.

Axonal degeneration is a key and early pathological feature in traumatic and neurodegenerative disorders of the CNS. Following a focal lesion to axons, extended axonal disintegration by acute axonal degeneration (AAD) occurs within several hours. During AAD, the accumulation of autophagic proteins including Unc-51 like autophagy activating kinase 1 (ULK1) has been demonstrated, but its role is incompletely understood. Read More

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http://dx.doi.org/10.1038/s41418-020-0543-yDOI Listing

The apoptosome molecular timer synergises with XIAP to suppress apoptosis execution and contributes to prognosticating survival in colorectal cancer.

Cell Death Differ 2020 Apr 27. Epub 2020 Apr 27.

Institute for Cell Biology and Immunology, Allmandring 31, 70569, Stuttgart, Germany.

The execution phase of apoptosis is a critical process in programmed cell death in response to a multitude of cellular stresses. A crucial component of this pathway is the apoptosome, a platform for the activation of pro-caspase 9 (PC9). Recent findings have shown that autocleavage of PC9 to Caspase 9 (C9) p35/p12 not only permits XIAP-mediated C9 inhibition but also temporally shuts down apoptosome activity, forming a molecular timer. Read More

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http://dx.doi.org/10.1038/s41418-020-0545-9DOI Listing

Hippo kinases MST1 and MST2 control the differentiation of the epididymal initial segment via the MEK-ERK pathway.

Cell Death Differ 2020 Apr 24. Epub 2020 Apr 24.

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.

Although the roles of the Hippo pathway in organogenesis and tumorigenesis have been well studied in multiple organs, its role in sperm maturation and male fertility has not been investigated. The initial segment (IS) of the epididymis plays a critical role in sperm maturation. IS differentiation is governed by ERK1/2, but the mechanisms of ERK1/2 activation in IS are not fully understood. Read More

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http://dx.doi.org/10.1038/s41418-020-0544-xDOI Listing

HSPA12A attenuates lipopolysaccharide-induced liver injury through inhibiting caspase-11-mediated hepatocyte pyroptosis via PGC-1α-dependent acyloxyacyl hydrolase expression.

Cell Death Differ 2020 Apr 24. Epub 2020 Apr 24.

Department of Geriatrics, Jiangsu Provincial Key Laboratory of Geriatrics, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

Liver dysfunction is strongly associated with poor survival of sepsis patients. Cytosolic lipopolysaccharide (LPS) sensing by Caspase-4/5/11 for pyroptosis activation is a major driver of the development of sepsis. Studies in macrophages and endothelial cells have demonstrated that LPS is inactivated by acyloxyacyl hydrolase (AOAH) and leading to desensitizing Caspase-4/5/11 to LPS. Read More

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http://dx.doi.org/10.1038/s41418-020-0536-xDOI Listing

The deubiquitylase USP2 maintains ErbB2 abundance via counteracting endocytic degradation and represents a therapeutic target in ErbB2-positive breast cancer.

Cell Death Differ 2020 Apr 23. Epub 2020 Apr 23.

Second Affiliated Hospital, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.

ErbB2 overexpression identifies a subclass of breast cancer as ErbB2-positive that is frequently associated with poor prognosis. Current ErbB2-targeted therapies have profoundly improved patient outcomes, but mutations occurring in ErbB2 have been shown to confer drug resistance. Induction of ErbB2 degradation was proposed as an intriguing strategy to battle with ErbB2-positive breast cancer and reduced mutation-incurred drug resistance. Read More

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http://dx.doi.org/10.1038/s41418-020-0538-8DOI Listing
April 2020
8.184 Impact Factor

The SCF ubiquitin ligase complex modulates TRAIL-R2-induced apoptosis by regulating FLIP(L).

Cell Death Differ 2020 Apr 20. Epub 2020 Apr 20.

Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.

TRAIL-R2 (DR5) is a clinically-relevant therapeutic target and a key target for immune effector cells. Herein, we identify a novel interaction between TRAIL-R2 and the Skp1-Cullin-1-F-box (SCF) Cullin-Ring E3 Ubiquitin Ligase complex containing Skp2 (SCF). We find that SCF can interact with both TRAIL-R2's pre-ligand association complex (PLAC) and ligand-activated death-inducing signalling complex (DISC). Read More

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http://dx.doi.org/10.1038/s41418-020-0539-7DOI Listing

Deficiency in fibroblast PPARβ/δ reduces nonmelanoma skin cancers in mice.

Cell Death Differ 2020 Apr 20. Epub 2020 Apr 20.

School of Biological Sciences, Nanyang Technological University Singapore, 60 Nanyang Drive, Singapore, 637551, Singapore.

The incidence of nonmelanoma skin cancer (NMSC) has been increasing worldwide. Most studies have highlighted the importance of cancer-associated fibroblasts (CAFs) in NMSC progression. However much less is known about the communication between normal fibroblasts and epithelia; disruption of this communication affects tumor initiation and the latency period in the emergence of tumors. Read More

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http://dx.doi.org/10.1038/s41418-020-0535-yDOI Listing