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Cell Death and Differentiation

Colin Hockings, Sweta Iyer, Rachel T Uren, Ruth M Kluck
No abstract text is available yet for this article.
February 13, 2019: Cell Death and Differentiation
Chunjia Li, Hongyu Chen, Zhou Lan, Shaozong He, Rongrong Chen, Fang Wang, Zhibo Liu, Kai Li, Lili Cheng, Ye Liu, Kun Sun, Xiaofeng Wan, Xinxin Chen, Haiyong Peng, Li Li, Yanjun Zhang, Yanling Jing, Min Huang, Yanan Wang, Yan Wang, Jiandong Jiang, Xiaojun Zha, Ligong Chen, Hongbing Zhang
Loss of either TSC1 or TSC2 causes tuberous sclerosis complex (TSC) via activation of mTOR signaling pathway. The two prominent features of TSC are skin lesions including hypomelanic macules and benign tumors in multiple organs, whose molecular alterations are largely unknown. We report here that Xc - cystine/glutamate antiporter (xCT) was elevated in Tsc2-/- or Pten-/- cells, Tsc1 knockout mouse tissues and TSC2-deficient human kidney tumor. xCT was transcriptionally boosted by mTOR-mediated Oct1 signaling cascade...
February 13, 2019: Cell Death and Differentiation
Chenling Meng, Jinyue Liao, Danfeng Zhao, Huihui Huang, Jinzhong Qin, Tin-Lap Lee, Degui Chen, Wai-Yee Chan, Yin Xia
Lethal (3) malignant brain tumor like 2 (L3MBTL2) is a member of the MBT-domain proteins, which are involved in transcriptional repression and implicated in chromatin compaction. Our previous study has shown that L3MBTL2 is highly expressed in the testis, but its role in spermatogenesis remains unclear. In the present study, we found that L3MBTL2 was most highly expressed in pachytene spermatocytes within the testis. Germ cell-specific ablation of L3mbtl2 in the testis led to increased abnormal spermatozoa, progressive decrease of sperm counts and premature testicular failure in mice...
February 13, 2019: Cell Death and Differentiation
Tanja Frank, Marcel Tuppi, Manuela Hugle, Volker Dötsch, Sjoerd J L van Wijk, Simone Fulda
Resistance to apoptosis is a hallmark of cancer and deregulation of apoptosis often leads to chemoresistance. Therefore, new approaches to target apoptosis-resistant cancer cells are crucial for the development of directed cancer therapies. In the present study, we investigated the effect of cell cycle regulators on interferon (IFN)-induced necroptosis as an alternative cell death mechanism to overcome apoptosis resistance. Here, we report a novel combination treatment of IFNs with cell cycle arrest-inducing compounds that induce necroptosis in apoptosis-resistant cancer cells and elucidate the underlying molecular mechanisms...
February 11, 2019: Cell Death and Differentiation
Thanh Kha Phan, Scott A Williams, Guneet K Bindra, Fung T Lay, Ivan K H Poon, Mark D Hulett
Phosphorylated phosphatidylinositol lipids, or phosphoinositides, critically regulate diverse cellular processes, including signalling transduction, cytoskeletal reorganisation, membrane dynamics and cellular trafficking. However, phosphoinositides have been inadequately investigated in the context of cell death, where they are mainly regarded as signalling secondary messengers. However, recent studies have begun to highlight the importance of phosphoinositides in facilitating cell death execution. Here, we cover the latest phosphoinositide research with a particular focus on phosphoinositides in the mechanisms of cell death...
February 11, 2019: Cell Death and Differentiation
Roberto Bravo-Sagua, Valentina Parra, Carolina Ortiz-Sandoval, Mario Navarro-Marquez, Andrea E Rodríguez, Natalia Diaz-Valdivia, Carlos Sanhueza, Camila Lopez-Crisosto, Nasser Tahbaz, Beverly A Rothermel, Joseph A Hill, Mariana Cifuentes, Thomas Simmen, Andrew F G Quest, Sergio Lavandero
Following publication of the article, the authors wrote to point out the following mistake.
February 11, 2019: Cell Death and Differentiation
Xiaojin Zhang, Xuan Chen, Tao Qi, Qiuyue Kong, Hao Cheng, Xiaofei Cao, Yuehua Li, Chuanfu Li, Li Liu, Zhengnian Ding
Obesity is one of the most serious public health problems. Peroxisome proliferator-activated receptor γ (PPARγ) plays the master role in adipocyte differentiation for obesity development. However, optimum anti-obesity drug has yet been developed, mandating more investigation to identify novel regulator in obesity pathogenesis. Heat shock protein 12A (HSPA12A) encodes a novel member of the HSP70 family. Here, we report that obese patients showed increased adipose HSPA12A expression, which was positively correlated with increase of body mass index...
February 11, 2019: Cell Death and Differentiation
Nina Germic, Ziva Frangez, Shida Yousefi, Hans-Uwe Simon
Autophagy is an evolutionally conserved, highly regulated catabolic process that combines cellular functions required for the regulation of metabolic balance under conditions of stress with those needed for the degradation of damaged cell organelles via the lysosomal machinery. The importance of autophagy for cell homeostasis and survival has long been appreciated. Recent data suggest that autophagy is also involved in non-metabolic functions that impact the immune system. Here, we reflect in two review articles the recent literature pointing to an important role for autophagy in innate immune cells...
February 8, 2019: Cell Death and Differentiation
Aarif Siddiqui, Paradesi Naidu Gollavilli, Annemarie Schwab, Maria Eleni Vazakidou, Pelin G Ersan, Mallika Ramakrishnan, Dick Pluim, Si'Ana Coggins, Ozge Saatci, Laura Annaratone, Jan Hm Schellens, Baek Kim, Irfan Ahmed Asangani, Suhail Ahmed Kabeer Rasheed, Caterina Marchiò, Ozgur Sahin, Paolo Ceppi
Cancer cells frequently boost nucleotide metabolism (NM) to support their increased proliferation, but the consequences of elevated NM on tumor de-differentiation are mostly unexplored. Here, we identified a role for thymidylate synthase (TS), a NM enzyme and established drug target, in cancer cell de-differentiation and investigated its clinical significance in breast cancer (BC). In vitro, TS knockdown increased the population of CD24+ differentiated cells, and attenuated migration and sphere-formation. RNA-seq profiling indicated repression of epithelial-to-mesenchymal transition (EMT) signature genes upon TS knockdown, and TS-deficient cells showed an increased ability to invade and metastasize in vivo, consistent with the occurrence of a partial EMT phenotype...
February 8, 2019: Cell Death and Differentiation
Yang Li, Dongcheng Feng, Zhanyu Wang, Yan Zhao, Ruimin Sun, Donghai Tian, Deshun Liu, Feng Zhang, Shili Ning, Jihong Yao, Xiaofeng Tian
Ferroptosis is a recently identified form of regulated cell death defined by the iron-dependent accumulation of lipid reactive oxygen species. Ferroptosis has been studied in various diseases such as cancer, Parkinson's disease, and stroke. However, the exact function and mechanism of ferroptosis in ischemia/reperfusion (I/R) injury, especially in the intestine, remains unknown. Considering the unique conditions required for ferroptosis, we hypothesize that ischemia promotes ferroptosis immediately after intestinal reperfusion...
February 8, 2019: Cell Death and Differentiation
Nina Germic, Ziva Frangez, Shida Yousefi, Hans-Uwe Simon
Autophagy is well equipped functionally to isolate microbial pathogens in autophagosomes and to carry out their clearance by dismemberment in the course of catabolic processes in the lysosome. Clearly, this is a non-metabolic function of autophagy that impacts strongly on the immune system. While in a preceding article on neutrophils, eosinophils, mast cells, and natural killer cells our focus was on the role of autophagy in regulating innate immune cell differentiation, degranulation, phagocytosis and extracellular trap formation, here we discuss monocytes/macrophages and dendritic cells, specifically, the influence of autophagy on functional cellular responses, such as phagocytosis, antigen presentation, cytokine production, control of inflammasome activation, tolerance and the consequences for overall host defense...
February 8, 2019: Cell Death and Differentiation
Vishva M Dixit
Vishva M. Dixit, M.D., Vice President of Physiological Chemistry at Genentech, Inc. has made many contributions to biomedicine, and his early work on apoptosis is prominent in introductory textbooks of biology and medicine.He is a member of the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences, and a Foreign Member, European Molecular Biology Organization.Additionally, he serves on the Boards of the Gates Foundation, Howard Hughes Medical Institute, and Keystone Symposia...
February 8, 2019: Cell Death and Differentiation
Francesca Nazio, Matteo Bordi, Valentina Cianfanelli, Franco Locatelli, Francesco Cecconi
Autophagy and mitophagy act in cancer as bimodal processes, whose differential functions strictly depend on cancer ontogenesis, progression, and type. For instance, they can act to promote cancer progression by helping cancer cells survive stress or, instead, when mutated or abnormal, to induce carcinogenesis by influencing cell signaling or promoting intracellular toxicity. For this reason, the study of autophagy in cancer is the main focus of many researchers and several clinical trials are already ongoing to manipulate autophagy and by this way determine the outcome of disease therapy...
February 6, 2019: Cell Death and Differentiation
Ataman Sendoel, Deni Subasic, Luca Ducoli, Martin Keller, Erich Michel, Ines Kohler, Kapil Dev Singh, Xue Zheng, Anneke Brümmer, Jochen Imig, Shivendra Kishore, Yibo Wu, Alexander Kanitz, Andres Kaech, Nitish Mittal, Ana M Matia-González, André P Gerber, Mihaela Zavolan, Ruedi Aebersold, Jonathan Hall, Frédéric H-T Allain, Michael O Hengartner
Post-transcriptional control of mRNAs by RNA-binding proteins (RBPs) has a prominent role in the regulation of gene expression. RBPs interact with mRNAs to control their biogenesis, splicing, transport, localization, translation, and stability. Defects in such regulation can lead to a wide range of human diseases from neurological disorders to cancer. Many RBPs are conserved between Caenorhabditis elegans and humans, and several are known to regulate apoptosis in the adult C. elegans germ line. How these RBPs control apoptosis is, however, largely unknown...
February 6, 2019: Cell Death and Differentiation
Maria Chiara Maiuri, Guido Kroemer
The relentless efforts of thousands of researchers have allowed deciphering the molecular machinery that regulates and executes autophagy, thus identifying multiple molecular targets to enhance or block the process, rendering autophagy "druggable". Autophagy inhibition may be useful for preserving the life of cells that otherwise would succumb to excessive self-digestion. Moreover, autophagy blockade may reduce the fitness of cancer cells or interrupt metabolic circuitries required for their growth...
February 6, 2019: Cell Death and Differentiation
Jialiang Shao, Jiongjiong Lu, Wencheng Zhu, Hua Yu, Xiaoqian Jing, Yi-Lin Wang, Xiang Wang, Xiong-Jun Wang
TP53 is the most frequently mutated gene in human cancer, whereas tumors with wild-type TP53 develop alternative strategies to survive. Identifying new regulators of p53 reactivation would greatly contribute to the development of cancer therapies. After screening the entire genome in liver cancer cells, we identified lysyl oxidase-like 4 (LOXL4) as a novel regulator for p53 activation. We found that 5-azacytidine (5-aza-CR) induces LOXL4 upregulation, with LOXL4 subsequently binding the basic domain of p53 via its low-isoelectric point region...
February 6, 2019: Cell Death and Differentiation
Hairui Yuan, Xiaowei Xu, Xue Feng, Endong Zhu, Jie Zhou, Guannan Wang, Lijie Tian, Baoli Wang
Long noncoding RNAs (LncRNAs) have been implicated in the regulation of adipocyte and osteoblast differentiation. However, the functional contributions of LncRNAs to adipocyte or osteoblast differentiation remain largely unexplored. In the current study we have identified a novel LncRNA named peroxisome proliferator-activated receptor γ coactivator-1β-OT1 (PGC1β-OT1). The expression levels of PGC1β-OT1 were altered during adipogenic and osteogenic differentiation from progenitor cells. 5'- and 3'-rapid amplification of cDNA ends (RACE) revealed that PGC1β-OT1 is 1759 nt in full length...
February 6, 2019: Cell Death and Differentiation
Alessandra di Gennaro, Valentina Damiano, Giulia Brisotto, Michela Armellin, Tiziana Perin, Antonella Zucchetto, Michela Guardascione, Herman P Spaink, Claudio Doglioni, B Ewa Snaar-Jagalska, Manuela Santarosa, Roberta Maestro
Since publication of the article, the authors were notified by ATCC that the cell line HCC1395 (ATCC® CRL-2324™ Lot 62235652) suffered a "low level of cell line cross-contamination" with another cell line.
February 6, 2019: Cell Death and Differentiation
Mohammed Salama, Diego Benitez-Riquelme, Seham Elabd, Leonel Munoz, Ping Zhang, Matthias Glanemann, Maria Caterina Mione, Robert Goldin, Thierry Soussi, Gary Davidson, Christine Blattner
p53 is one of the most important tumour suppressor proteins currently known. It is activated in response to DNA damage and this activation leads to proliferation arrest and cell death. The abundance and activity of p53 are tightly controlled and reductions in p53's activity can contribute to the development of cancer. Here, we show that Fam83F increases p53 protein levels by protein stabilisation. Fam83F interacts with p53 and decreases its ubiquitination and degradation. Fam83F is induced in response to DNA damage and its overexpression also increases p53 activity in cell culture experiments and in zebrafish embryos...
January 28, 2019: Cell Death and Differentiation
Marco B Schaaf, Diede Houbaert, Odeta Meçe, Patrizia Agostinis
In mammalian cells, autophagy is the major pathway for the degradation and recycling of obsolete and potentially noxious cytoplasmic materials, including proteins, lipids, and whole organelles, through the lysosomes. Autophagy maintains cellular and tissue homeostasis and provides a mechanism to adapt to extracellular cues and metabolic stressors. Emerging evidence unravels a critical function of autophagy in endothelial cells (ECs), the major components of the blood vasculature, which delivers nutrients and oxygen to the parenchymal tissue...
January 28, 2019: Cell Death and Differentiation
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