
样式: 排序: IF: - GO 导出 标记为已读
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RhoA signaling increases mitophagy and protects cardiomyocytes against ischemia by stabilizing PINK1 protein and recruiting Parkin to mitochondria Cell Death Differ. (IF 8.086) Pub Date : 2022-06-27 Michelle Tu, Valerie P. Tan, Justin D. Yu, Raghav Tripathi, Zahna Bigham, Melissa Barlow, Jeffrey M. Smith, Joan Heller Brown, Shigeki Miyamoto
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Past, present, and future perspectives of transcription factor EB (TFEB): mechanisms of regulation and association with disease Cell Death Differ. (IF 8.086) Pub Date : 2022-06-23 Anderson Tan, Renuka Prasad, Chaerin Lee, Eek-hoon Jho
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dsDNA-induced AIM2 pyroptosis halts aberrant inflammation during rhabdomyolysis-induced acute kidney injury Cell Death Differ. (IF 8.086) Pub Date : 2022-06-23 Chintogtokh Baatarjav, Takanori Komada, Tadayoshi Karasawa, Naoya Yamada, Ariunaa Sampilvanjil, Takayoshi Matsumura, Masafumi Takahashi
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Aberrant activation of p53/p66Shc-mInsc axis increases asymmetric divisions and attenuates proliferation of aged mammary stem cells Cell Death Differ. (IF 8.086) Pub Date : 2022-06-23 Chiara Priami, Daniela Montariello, Giulia De Michele, Federica Ruscitto, Andrea Polazzi, Simona Ronzoni, Giovanni Bertalot, Giorgio Binelli, Valentina Gambino, Lucilla Luzi, Marina Mapelli, Marco Giorgio, Enrica Migliaccio, Pier Giuseppe Pelicci
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CEND1 deficiency induces mitochondrial dysfunction and cognitive impairment in Alzheimer’s disease Cell Death Differ. (IF 8.086) Pub Date : 2022-06-22 Wenting Xie, Dong Guo, Jieyin Li, Lei Yue, Qi Kang, Guimiao Chen, Tingwen Zhou, Han Wang, Kai Zhuang, Lige Leng, Huifang Li, Zhenyi Chen, Weiwei Gao, Jie Zhang
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Ca2+-mediated mitochondrial inner membrane permeabilization induces cell death independently of Bax and Bak Cell Death Differ. (IF 8.086) Pub Date : 2022-06-20 Giovanni Quarato, Fabien Llambi, Cliff S. Guy, Jaeki Min, Marisa Actis, Huan Sun, Shilpa Narina, Shondra M. Pruett-Miller, Junmin Peng, Zoran Rankovic, Douglas R. Green
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Designed Ankyrin Repeat Proteins as a tool box for analyzing p63 Cell Death Differ. (IF 8.086) Pub Date : 2022-06-18 Alexander Strubel, Philipp Münick, Apirat Chaikuad, Birgit Dreier, Jonas Schaefer, Jakob Gebel, Christian Osterburg, Marcel Tuppi, Birgit Schäfer, Stefan Knapp, Andreas Plückthun, Volker Dötsch
The function of the p53 transcription factor family is dependent on several folded domains. In addition to a DNA-binding domain, members of this family contain an oligomerization domain. p63 and p73 also contain a C-terminal Sterile α-motif domain. Inhibition of most transcription factors is difficult as most of them lack deep pockets that can be targeted by small organic molecules. Genetic knock-out
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B7-1 mediates podocyte injury and glomerulosclerosis through communication with Hsp90ab1-LRP5-β-catenin pathway Cell Death Differ. (IF 8.086) Pub Date : 2022-06-16 Jiemei Li, Jing Niu, Wenjian Min, Jun Ai, Xu Lin, Jinhua Miao, Shan Zhou, Ye Liang, Shuangqin Chen, Qian Ren, Kunyu Shen, Qinyu Wu, Xiaolong Li, Weiwei Shen, Fan Fan Hou, Youhua Liu, Peng Yang, Lili Zhou
Podocyte injury is a hallmark of glomerular diseases; however, the underlying mechanisms remain unclear. B7-1 is increased in injured podocytes, but its intrinsic role is controversial. The clinical data here revealed the intimate correlation of urinary B7-1 with severity of glomerular injury. Through transcriptomic and biological assays in B7-1 transgenic and adriamycin nephropathy models, we identified
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Ptpn1 deletion protects oval cells against lipoapoptosis by favoring lipid droplet formation and dynamics Cell Death Differ. (IF 8.086) Pub Date : 2022-06-09 Inés Barahona, Patricia Rada, Silvia Calero-Pérez, Ruben Grillo-Risco, Laura Pereira, M. Carmen Soler-Vázquez, Laura María LaIglesia, María J. Moreno-Aliaga, Laura Herrero, Dolors Serra, Carmelo García-Monzon, Águeda González-Rodriguez, Jesús Balsinde, Francisco García-García, M. Pilar Valdecantos, Ángela M. Valverde
Activation of oval cells (OCs) has been related to hepatocyte injury during chronic liver diseases including non-alcoholic fatty liver disease (NAFLD). However, OCs plasticity can be affected under pathological environments. We previously found protection against hepatocyte cell death by inhibiting protein tyrosine phosphatase 1B (PTP1B). Herein, we investigated the molecular and cellular processes
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DJ-1 binds to Rubicon to Impair LC-3 Associated Phagocytosis Cell Death Differ. (IF 8.086) Pub Date : 2022-05-31 Sahil Gupta, Hajera Amatullah, James N. Tsoporis, Kuiru Wei, Ana Paula Teixeira Monteiro, Amin M. Ektesabi, Amir K. Varkouhi, Chirag M. Vaswani, Amanda Formosa, Alexandre T. Fabro, Sri Nagarjun Batchu, Chris Fjell, James A. Russell, Keith R. Walley, Andrew Advani, Thomas G. Parker, John C. Marshall, Patricia R. M. Rocco, Gregory D. Fairn, Tak Wah Mak, Claudia C. dos Santos
The ability to effectively clear infection is fundamental to host survival. Sepsis, defined as dysregulated host response to infection, is a heterogenous clinical syndrome that does not uniformly clear intact bacterial or sterile infection (i.e., lipopolysaccharide). These findings were further associated with increased survival in DJ-1 deficient animals exposed to intact bacteria relative to DJ-1
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BAP1 promotes the repair of UV-induced DNA damage via PARP1-mediated recruitment to damage sites and control of activity and stability Cell Death Differ. (IF 8.086) Pub Date : 2022-05-30 Shin-Ai Lee, Daye Lee, Minhwa Kang, Sora Kim, Su-Jung Kwon, Han-Sae Lee, Hye-Ran Seo, Prashant Kaushal, Nam Soo Lee, Hongtae Kim, Cheolju Lee, Jongbum Kwon
BRCA1-associated protein-1 (BAP1) is a ubiquitin C-terminal hydrolase domain-containing deubiquitinase with tumor suppressor activity. The gene encoding BAP1 is mutated in various human cancers, with particularly high frequency in kidney and skin cancers, and BAP1 is involved in many cancer-related cellular functions, such as DNA repair and genome stability. Although BAP1 stimulates DNA double-strand
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A truncating variant of RAD51B associated with primary ovarian insufficiency provides insights into its meiotic and somatic functions Cell Death Differ. (IF 8.086) Pub Date : 2022-05-27 Monica M. Franca, Yazmine B. Condezo, Maëva Elzaiat, Natalia Felipe-Medina, Fernando Sánchez-Sáez, Sergio Muñoz, Raquel Sainz-Urruela, M. Rosario Martín-Hervás, Rodrigo García-Valiente, Manuel A. Sánchez-Martín, Aurora Astudillo, Juan Mendez, Elena Llano, Reiner A. Veitia, Berenice B. Mendonca, Alberto M. Pendás
Primary ovarian insufficiency (POI) causes female infertility by abolishing normal ovarian function. Although its genetic etiology has been extensively investigated, most POI cases remain unexplained. Using whole-exome sequencing, we identified a homozygous variant in RAD51B –(c.92delT) in two sisters with POI. In vitro studies revealed that this variant leads to translation reinitiation at methionine
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Acetylation licenses Th1 cell polarization to constrain Listeria monocytogenes infection Cell Death Differ. (IF 8.086) Pub Date : 2022-05-25 Yanan Sophia Zhang, Dazhuan Eric Xin, Zhizhang Wang, Wenlong Peng, Yuanyuan Zeng, Jianshu Liang, Mengmeng Xu, Nannan Chen, Jie Zhang, Jicheng Yue, Mengtao Cao, Chenxi Zhang, Yuting Wang, Zhijie Chang, Xiao-mei Lu, Lei Chang, Y. Eugene Chinn
T helper 1 (Th1) immunity is typically viewed as a critical adaptation by vertebrates against intracellular pathogens. Identifying novel targets to enhance Th1 cell differentiation and function is increasingly important for anti-infection immunity. Here, through small-molecule screening focusing on epigenetic modifiers during the in vitro Th1 cell differentiation process, we identified that the selective
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The mitochondrial chaperone TRAP1 regulates F-ATP synthase channel formation Cell Death Differ. (IF 8.086) Pub Date : 2022-05-25 Giuseppe Cannino, Andrea Urbani, Marco Gaspari, Mariaconcetta Varano, Alessandro Negro, Antonio Filippi, Francesco Ciscato, Ionica Masgras, Christoph Gerle, Elena Tibaldi, Anna Maria Brunati, Giorgio Colombo, Giovanna Lippe, Paolo Bernardi, Andrea Rasola
Binding of the mitochondrial chaperone TRAP1 to client proteins shapes bioenergetic and proteostatic adaptations of cells, but the panel of TRAP1 clients is only partially defined. Here we show that TRAP1 interacts with F-ATP synthase, the protein complex that provides most cellular ATP. TRAP1 competes with the peptidyl-prolyl cis-trans isomerase cyclophilin D (CyPD) for binding to the oligomycin
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Plin2-mediated lipid droplet mobilization accelerates exit from pluripotency by lipidomic remodeling and histone acetylation Cell Death Differ. (IF 8.086) Pub Date : 2022-05-25 Yi Wu, Keshi Chen, Linpeng Li, Zhihong Hao, Tianyu Wang, Yang Liu, Guangsuo Xing, Zichao Liu, Heying Li, Hao Yuan, Jianghuan Lu, Cheng Zhang, Jinye Zhang, Danyun Zhao, Junwei Wang, Jinfu Nie, Dan Ye, Guangjin Pan, Wai-Yee Chan, Xingguo Liu
Metabolic switch is critical for cell fate determination through metabolic functions, epigenetic modifications, and gene expression. However, the mechanisms underlying these alterations and their functional roles remain unclear. Here, we show that Plin2-mediated moderate lipid hydrolysis is critical for pluripotency of embryonic stem cells (ESCs). Upon exit from pluripotency, lipid droplet (LD)-associated
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Epithelial de-differentiation triggered by co-ordinate epigenetic inactivation of the EHF and CDX1 transcription factors drives colorectal cancer progression Cell Death Differ. (IF 8.086) Pub Date : 2022-05-23 Ian Y. Luk, Laura J. Jenkins, Kael L. Schoffer, Irvin Ng, Janson W. T. Tse, Dmitri Mouradov, Stanislaw Kaczmarczyk, Rebecca Nightingale, Allan D. Burrows, Robin L. Anderson, Diego Arango, Higinio Dopeso, Larry Croft, Mark F. Richardson, Oliver M. Sieber, Yang Liao, Jennifer K. Mooi, Natalia Vukelic, Camilla M. Reehorst, Shoukat Afshar-Sterle, Vicki L. J. Whitehall, Lochlan Fennell, Helen E. Abud, Niall
Colorectal cancers (CRCs) often display histological features indicative of aberrant differentiation but the molecular underpinnings of this trait and whether it directly drives disease progression is unclear. Here, we identify co-ordinate epigenetic inactivation of two epithelial-specific transcription factors, EHF and CDX1, as a mechanism driving differentiation loss in CRCs. Re-expression of EHF
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Apoptotic priming is defined by the dynamic exchange of Bcl-2 proteins between mitochondria and cytosol Cell Death Differ. (IF 8.086) Pub Date : 2022-05-18 Louise E. King, Ricardo Rodriguez-Enriquez, Robert Pedley, Charlotte E. L. Mellor, Pengbo Wang, Egor Zindy, Michael R. H. White, Keith Brennan, Andrew P. Gilmore
Apoptosis is regulated by interactions between the BH3-only and multi-domain Bcl-2 family proteins. These interactions are integrated on the outer mitochondrial membrane (OMM) where they set the threshold for apoptosis, known as mitochondrial priming. However, how mitochondrial priming is controlled at the level of single cells remains unclear. Retrotranslocation of Bcl-XL has been proposed as one
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Immune response in COVID-19: what is next? Cell Death Differ. (IF 8.086) Pub Date : 2022-05-17 Qing Li, Ying Wang, Qiang Sun, Jasmin Knopf, Martin Herrmann, Liangyu Lin, Jingting Jiang, Changshun Shao, Peishan Li, Xiaozhou He, Fei Hua, Zubiao Niu, Chaobing Ma, Yichao Zhu, Giuseppe Ippolito, Mauro Piacentini, Jerome Estaquier, Sonia Melino, Felix Daniel Weiss, Emanuele Andreano, Eicke Latz, Joachim L. Schultze, Rino Rappuoli, Alberto Mantovani, Tak Wah Mak, Gerry Melino, Yufang Shi
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Ezh2 competes with p53 to license lncRNA Neat1 transcription for inflammasome activation Cell Death Differ. (IF 8.086) Pub Date : 2022-05-14 Jia Yuan, Qingchen Zhu, Xingli Zhang, Zhenzhen Wen, Guiheng Zhang, Ni Li, Yifei Pei, Yan Wang, Siyu Pei, Jing Xu, Pan Jia, Chao Peng, Wei Lu, Jun Qin, Qian Cao, Yichuan Xiao
Inflammasome contributes to the pathogenesis of various inflammatory diseases, but the epigenetic mechanism controlling its activation remains elusive. Here, we found that the histone methyltransferase Ezh2 mediates the activation of multiple types of inflammasomes in macrophages/microglia independent of its methyltransferase activity and thus promotes inflammasome-related pathologies. Mechanistically
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Loss of RBMS1 promotes anti-tumor immunity through enabling PD-L1 checkpoint blockade in triple-negative breast cancer Cell Death Differ. (IF 8.086) Pub Date : 2022-05-10 Jinrui Zhang, Ge Zhang, Wenjing Zhang, Lu Bai, Luning Wang, Tiantian Li, Li Yan, Yang Xu, Dan Chen, Wenting Gao, Chuanzhou Gao, Chaoqun Chen, Menglin Ren, Yuexia Jiao, Hongqiang Qin, Yu Sun, Lili Zhi, Yangfan Qi, Jinyao Zhao, Quentin Liu, Han Liu, Yang Wang
Immunotherapy has been widely utilized in multiple tumors, however, its efficacy in the treatment of triple-negative breast cancers (TNBC) is still being challenged. Meanwhile, functions and mechanisms of RNA binding proteins in regulating immunotherapy for TNBC remain largely elusive. Here we reported that the RNA binding protein RBMS1 is prevalent among immune-cold TNBC. Through a systematic shRNA-mediated
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A viral interferon regulatory factor degrades RNA-binding protein hnRNP Q1 to enhance aerobic glycolysis via recruiting E3 ubiquitin ligase KLHL3 and decaying GDPD1 mRNA Cell Death Differ. (IF 8.086) Pub Date : 2022-05-10 Xiaoyu Qi, Qin Yan, Yuancui Shang, Runran Zhao, Xiangya Ding, Shou-Jiang Gao, Wan Li, Chun Lu
Reprogramming of host metabolism is a common strategy of viral evasion of host cells, and is essential for successful viral infection and induction of cancer in the context cancer viruses. Kaposi’s sarcoma (KS) is the most common AIDS-associated cancer caused by KS-associated herpesvirus (KSHV) infection. KSHV-encoded viral interferon regulatory factor 1 (vIRF1) regulates multiple signaling pathways
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Wnt/beta-catenin signaling confers ferroptosis resistance by targeting GPX4 in gastric cancer Cell Death Differ. (IF 8.086) Pub Date : 2022-05-09 Yue Wang, Lixin Zheng, Wenjing Shang, Zongcheng Yang, Tongyu Li, Fen Liu, Wei Shao, Lin Lv, Li Chai, Lingxin Qu, Qing Xu, Jie Du, Xiuming Liang, Jiping Zeng, Jihui Jia
The development of chemotherapy resistance is the most vital obstacle to clinical efficacy in gastric cancer (GC). The dysregulation of the Wnt/beta-catenin signaling pathway is critically associated with GC development and chemotherapy resistance. Ferroptosis is a form of regulated cell death, induced by an iron-dependent accumulation of lipid peroxides during chemotherapy. However, whether the Wnt/beta-catenin
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RUNX2 recruits the NuRD(MTA1)/CRL4B complex to promote breast cancer progression and bone metastasis Cell Death Differ. (IF 8.086) Pub Date : 2022-05-09 Xin Yin, Xu Teng, Tianyu Ma, Tianshu Yang, Jingyao Zhang, Miaomiao Huo, Wei Liu, Yunkai Yang, Baowen Yuan, Hefen Yu, Wei Huang, Yan Wang
Runt-related transcription factor 2 (RUNX2) is an osteogenesis-related transcription factor that has emerged as a prominent transcription repressing factor in carcinogenesis. However, the role of RUNX2 in breast cancer metastasis remains poorly understood. Here, we show that RUNX2 recruits the metastasis-associated 1 (MTA1)/NuRD and the Cullin 4B (CUL4B)-Ring E3 ligase (CRL4B) complex to form a tr
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Atg6 promotes organismal health by suppression of cell stress and inflammation Cell Death Differ. (IF 8.086) Pub Date : 2022-05-06 James L. Shen, Johnna Doherty, Elizabeth Allen, Tina M. Fortier, Eric H. Baehrecke
Autophagy targets cytoplasmic materials for degradation, and influences cell health. Alterations in Atg6/Beclin-1, a key regulator of autophagy, are associated with multiple diseases. While the role of Atg6 in autophagy regulation is heavily studied, the role of Atg6 in organism health and disease progression remains poorly understood. Here, we discover that loss of Atg6 in Drosophila results in various
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Mitochondria supply sub-lethal signals for cytokine secretion and DNA-damage in H. pylori infection Cell Death Differ. (IF 8.086) Pub Date : 2022-05-03 Benedikt Dörflinger, Mohamed Tarek Badr, Aladin Haimovici, Lena Fischer, Juliane Vier, Arlena Metz, Bianca Eisele, Peter Bronsert, Konrad Aumann, Jens Höppner, Collins Waguia Kontchou, Ishita Parui, Arnim Weber, Susanne Kirschnek, Georg Häcker
The bacterium Helicobacter pylori induces gastric inflammation and predisposes to cancer. H. pylori-infected epithelial cells secrete cytokines and chemokines and undergo DNA-damage. We show that the host cell’s mitochondrial apoptosis system contributes to cytokine secretion and DNA-damage in the absence of cell death. H. pylori induced secretion of cytokines/chemokines from epithelial cells, dependent
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Targeting the miR-34a/LRPPRC/MDR1 axis collapse the chemoresistance in P53 inactive colorectal cancer Cell Death Differ. (IF 8.086) Pub Date : 2022-04-28 Yang Yang, Hongyu Yuan, Lianmei Zhao, Shichao Guo, Sijun Hu, Miaomiao Tian, Yongzhan Nie, Jiarui Yu, Chaoxi Zhou, Jian Niu, Guiying Wang, Yongmei Song
P53 mutation is an important cause of chemoresistance in colorectal cancer (CRC). The investigation and identification of the downstream targets and underlying molecular mechanism of chemoresistance induced by P53 abnormalities are therefore of great clinical significance. In this study, we demonstrated and reported for the first time that leucine-rich pentatricopeptide repeat-containing protein (LRPPRC)
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GSK3β mediates the spatiotemporal dynamics of NLRP3 inflammasome activation Cell Death Differ. (IF 8.086) Pub Date : 2022-04-27 Suyavaran Arumugam, Yanqin Qin, Ziwen Liang, Sheng-Na Han, S. L. Tejaswi Boodapati, Junzi Li, Qiuxia Lu, Richard A. Flavell, Wajahat Z. Mehal, Xinshou Ouyang
Subcellular machinery of NLRP3 is essential for inflammasome assembly and activation. However, the stepwise process and mechanistic basis of NLRP3 engagement with organelles remain unclear. Herein, we demonstrated glycogen synthase kinase 3β (GSK3β) as a molecular determinant for the spatiotemporal dynamics of NLRP3 inflammasome activation. Using live cell multispectral time-lapse tracking acquisition
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Increased apoptotic sensitivity of glioblastoma enables therapeutic targeting by BH3-mimetics Cell Death Differ. (IF 8.086) Pub Date : 2022-04-26 Anna L. Koessinger, Catherine Cloix, Dominik Koessinger, Dieter Henrik Heiland, Florian J. Bock, Karen Strathdee, Kevin Kinch, Laura Martínez-Escardó, Nikki R. Paul, Colin Nixon, Gaurav Malviya, Mark R. Jackson, Kirsteen J. Campbell, Katrina Stevenson, Sandeep Davis, Yassmin Elmasry, Asma Ahmed, Jim O’Prey, Gabriel Ichim, Oliver Schnell, William Stewart, Karen Blyth, Kevin M. Ryan, Anthony J. Chalmers
Glioblastoma (GBM) is the most prevalent malignant primary brain tumour in adults. GBM typically has a poor prognosis, mainly due to a lack of effective treatment options leading to tumour persistence or recurrence. We investigated the therapeutic potential of targeting anti-apoptotic BCL-2 proteins in GBM. Levels of anti-apoptotic BCL-xL and MCL-1 were consistently increased in GBM compared with non-malignant
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BAP1 shapes the bone marrow niche for lymphopoiesis by fine-tuning epigenetic profiles in endosteal mesenchymal stromal cells Cell Death Differ. (IF 8.086) Pub Date : 2022-04-26 Jinguk Jeong, Inkyung Jung, Ji-Hoon Kim, Shin Jeon, Do Young Hyeon, Hyungyu Min, Byeonggeun Kang, Jinwoo Nah, Daehee Hwang, Soo-Jong Um, Myunggon Ko, Rho Hyun Seong
Hematopoiesis occurs within a unique bone marrow (BM) microenvironment, which consists of various niche cells, cytokines, growth factors, and extracellular matrix components. These multiple components directly or indirectly regulate the maintenance and differentiation of hematopoietic stem cells (HSCs). Here we report that BAP1 in BM mesenchymal stromal cells (MSCs) is critical for the maintenance
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S-Nitrosylation of cathepsin B affects autophagic flux and accumulation of protein aggregates in neurodegenerative disorders Cell Death Differ. (IF 8.086) Pub Date : 2022-04-24 Ki-Ryeong Kim, Eun-Jung Cho, Jae-Won Eom, Sang-Seok Oh, Tomohiro Nakamura, Chang-ki Oh, Stuart A. Lipton, Yang-Hee Kim
Protein S-nitrosylation is known to regulate enzymatic function. Here, we report that nitric oxide (NO)-related species can contribute to Alzheimer’s disease (AD) by S-nitrosylating the lysosomal protease cathepsin B (forming SNO-CTSB), thereby inhibiting CTSB activity. This posttranslational modification inhibited autophagic flux, increased autolysosomal vesicles, and led to accumulation of protein
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Trim39 regulates neuronal apoptosis by acting as a SUMO-targeted E3 ubiquitin-ligase for the transcription factor NFATc3 Cell Death Differ. (IF 8.086) Pub Date : 2022-04-21 Meenakshi Basu-Shrivastava, Barbara Mojsa, Stéphan Mora, Ian Robbins, Guillaume Bossis, Iréna Lassot, Solange Desagher
NFATc3 is the predominant member of the NFAT family of transcription factors in neurons, where it plays a pro-apoptotic role. Mechanisms controlling NFAT protein stability are poorly understood. Here we identify Trim39 as an E3 ubiquitin-ligase of NFATc3. Indeed, Trim39 binds and ubiquitinates NFATc3 in vitro and in cells where it reduces NFATc3 protein level and transcriptional activity. In contrast
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IRF4 deficiency vulnerates B-cell progeny for leukemogenesis via somatically acquired Jak3 mutations conferring IL-7 hypersensitivity Cell Death Differ. (IF 8.086) Pub Date : 2022-04-22 Dennis Das Gupta, Christoph Paul, Nadine Samel, Maria Bieringer, Daniel Staudenraus, Federico Marini, Hartmann Raifer, Lisa Menke, Lea Hansal, Bärbel Camara, Edith Roth, Patrick Daum, Michael Wanzel, Marco Mernberger, Andrea Nist, Uta-Maria Bauer, Frederik Helmprobst, Malte Buchholz, Katrin Roth, Lorenz Bastian, Alina M. Hartmann, Claudia Baldus, Koichi Ikuta, Andreas Neubauer, Andreas Burchert, Hans-Martin
The processes leading from disturbed B-cell development to adult B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) remain poorly understood. Here, we describe Irf4−/− mice as prone to developing BCP-ALL with age. Irf4−/− preB-I cells exhibited impaired differentiation but enhanced proliferation in response to IL-7, along with reduced retention in the IL-7 providing bone marrow niche due to decreased
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Progranulin regulates the development and function of NKT2 cells through EZH2 and PLZF Cell Death Differ. (IF 8.086) Pub Date : 2022-04-21 Zuochen Du, Lu Huang, Xin Dai, Di Yang, Linlin Niu, Heather Miller, Changshun Ruan, Han Li, Leling Hu, Lijia Zhou, Ding Jian, Jian Sun, Xiaoqi Shi, Pei Huang, Yan Chen, Xiaodong Zhao, Chaohong Liu
T helper 2 (Th2) cytokine production by invariant natural killer T (iNKT) cells is involved in the development of asthma, but the regulation of Th2 cytokines in iNKT cells remains unknown. Although it is known that progranulin (PGRN) induces the production of Th2 cytokines in iNKT cells in vivo, the underlying mechanism is not clear. This study aims to investigate the role of PGRN in iNKT cells. The
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Selective ferroptosis vulnerability due to familial Alzheimer’s disease presenilin mutations Cell Death Differ. (IF 8.086) Pub Date : 2022-04-21 Mark A. Greenough, Darius J. R. Lane, Rachelle Balez, Helena Targa Dias Anastacio, Zhiwen Zeng, Katherine Ganio, Christopher A. McDevitt, Karla Acevedo, Abdel Ali Belaidi, Jari Koistinaho, Lezanne Ooi, Scott Ayton, Ashley I. Bush
Mutations in presenilin 1 and 2 (PS1 and PS2) cause autosomal dominant familial Alzheimer’s disease (FAD). Ferroptosis has been implicated as a mechanism of neurodegeneration in AD since neocortical iron burden predicts Alzheimer’s disease (AD) progression. We found that loss of the presenilins dramatically sensitizes multiple cell types to ferroptosis, but not apoptosis. FAD causal mutations of presenilins
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p53 at the crossroad of DNA replication and ribosome biogenesis stress pathways Cell Death Differ. (IF 8.086) Pub Date : 2022-04-20 Mikael S. Lindström, Jiri Bartek, Apolinar Maya-Mendoza
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Correction to: Prostate-specific oncogene OTUD6A promotes prostatic tumorigenesis via deubiquitinating and stabilizing c-Myc Cell Death Differ. (IF 8.086) Pub Date : 2022-04-19 Yunhua Peng,Jing Liu,Zhen Wang,Chunping Cui,Tiantian Zhang,Shuangxi Zhang,Peipei Gao,Zhanwu Hou,Huadong Liu,Jianping Guo,Jinfang Zhang,Yurong Wen,Wenyi Wei,Lingqiang Zhang,Jiankang Liu,Jiangang Long
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The phosphorylation and dephosphorylation switch of VCP/p97 regulates the architecture of centrosome and spindle Cell Death Differ. (IF 8.086) Pub Date : 2022-04-16 Kaiyuan Zhu, Yang Cai, Xiaotong Si, Zuodong Ye, Yuanzhu Gao, Chuang Liu, Rui Wang, Zhibin Ma, Huazhang Zhu, Liang Zhang, Shengjin Li, Hongmin Zhang, Jianbo Yue
The proper orientation of centrosome and spindle is essential for genome stability; however, the mechanism that governs these processes remains elusive. Here, we demonstrated that polo-like kinase 1 (Plk1), a key mitotic kinase, phosphorylates residue Thr76 in VCP/p97 (an AAA-ATPase), at the centrosome from prophase to anaphase. This phosphorylation process recruits VCP to the centrosome and in this
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Ubiquitin-binding domain in ABIN1 is critical for regulating cell death and inflammation during development Cell Death Differ. (IF 8.086) Pub Date : 2022-04-16 Ming Li, Yongbo Liu, Chengxian Xu, Qun Zhao, Jianling Liu, Mingyan Xing, Xiaoming Li, Haiwei Zhang, Xiaoxia Wu, Lingxia Wang, Yangjing Ou, Xuanhui Wu, Xiaoming Zhao, Han Liu, Lin Qiu, Fang Li, Jinbao Li, Wuwei Rong, Yan Luo, Jiangshan Deng, Xiuzhe Wang, Zhichao Wang, Yuwu Zhao, Ankang Lv, Qingfeng Li, Haibing Zhang
ABIN1 is a polyubiquitin-binding protein known to regulate NF-κB activation and cell death signaling. Mutations in Abin1 can cause severe immune diseases in human, such as psoriasis, systemic lupus erythematosus, and systemic sclerosis. Here, we generated mice that disrupted the ubiquitin-binding domain of ABIN1 (Abin1UBD/UBD) died during later embryogenesis owing to TNFR1-mediated cell death, similar
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Non-coding RNAs and ferroptosis: potential implications for cancer therapy Cell Death Differ. (IF 8.086) Pub Date : 2022-04-14 Amar Balihodzic, Felix Prinz, Michael A. Dengler, George A. Calin, Philipp J. Jost, Martin Pichler
Ferroptosis is a recently defined form of regulated cell death, which is biochemically and morphologically distinct from traditional forms of programmed cell death such as apoptosis or necrosis. It is driven by iron, reactive oxygen species, and phospholipids that are oxidatively damaged, ultimately resulting in mitochondrial damage and breakdown of membrane integrity. Numerous cellular signaling pathways
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O-GlcNAcylation and stablization of SIRT7 promote pancreatic cancer progression by blocking the SIRT7-REGγ interaction Cell Death Differ. (IF 8.086) Pub Date : 2022-04-14 Xiaoman He, Yongzhou Li, Qing Chen, Lei Zheng, Jianyao Lou, Chuanshuai Lin, Jiali Gong, Yi Zhu, Yulian Wu
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and its dismal prognosis indicates the urgent need to elucidate the potential oncogenic mechanisms. SIRT7 is a classic NAD+-dependent deacetylase that stabilizes the transformed state of cancer cells. However, its functional roles in PDAC are still unclear. Here, we found that SIRT7 expression is upregulated and predicts poor
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Chlamydia trachomatis inhibits apoptosis in infected cells by targeting the pro-apoptotic proteins Bax and Bak Cell Death Differ. (IF 8.086) Pub Date : 2022-04-09 Collins Waguia Kontchou, Ian E. Gentle, Arnim Weber, Axel Schoeniger, Frank Edlich, Georg Häcker
Apoptosis acts in defense against microbial infection, and many infectious agents have developed strategies to inhibit host cell apoptosis. The human pathogen Chlamydia trachomatis (Ctr) is an obligate intracellular bacterium that strongly inhibits mitochondrial apoptosis of its human host cell but there is no agreement how the bacteria achieve this. We here provide a molecular analysis of chlamydial
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Of the many cellular responses activated by TP53, which ones are critical for tumour suppression? Cell Death Differ. (IF 8.086) Pub Date : 2022-04-08 Annabella F. Thomas, Gemma L. Kelly, Andreas Strasser
The tumour suppressor TP53 is a master regulator of several cellular processes that collectively suppress tumorigenesis. The TP53 gene is mutated in ~50% of human cancers and these defects usually confer poor responses to therapy. The TP53 protein functions as a homo-tetrameric transcription factor, directly regulating the expression of ~500 target genes, some of them involved in cell death, cell cycling
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Tumor growth of neurofibromin-deficient cells is driven by decreased respiration and hampered by NAD+ and SIRT3 Cell Death Differ. (IF 8.086) Pub Date : 2022-04-07 Ionica Masgras, Giuseppe Cannino, Francesco Ciscato, Carlos Sanchez-Martin, Fereshteh Babaei Darvishi, Francesca Scantamburlo, Marco Pizzi, Alessio Menga, Dolores Fregona, Alessandra Castegna, Andrea Rasola
Neurofibromin loss drives neoplastic growth and a rewiring of mitochondrial metabolism. Here we report that neurofibromin ablation dampens expression and activity of NADH dehydrogenase, the respiratory chain complex I, in an ERK-dependent fashion, decreasing both respiration and intracellular NAD+. Expression of the alternative NADH dehydrogenase NDI1 raises NAD+/NADH ratio, enhances the activity of
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What can we learn from mice lacking pro-survival BCL-2 proteins to advance BH3 mimetic drugs for cancer therapy? Cell Death Differ. (IF 8.086) Pub Date : 2022-04-06 Kerstin Brinkmann, Ashley P. Ng, Carolyn A. de Graaf, Andreas Strasser
In many human cancers the control of apoptosis is dysregulated, for instance as a result of the overexpression of pro-survival BCL-2 proteins. This promotes tumorigenesis by protecting nascent neoplastic cells from stress and renders malignant cells resistant to anti-cancer agents. Therefore, several BH3 mimetic drugs targeting distinct pro-survival proteins have been developed. The BCL-2 inhibitor
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The genotypes and phenotypes of missense mutations in the proline domain of the p53 protein Cell Death Differ. (IF 8.086) Pub Date : 2022-04-05 David Hoyos, Benjamin Greenbaum, Arnold J. Levine
The p53 protein is structurally and functionally divided into five domains. The proline-rich domain is localized at amino acids 55–100. 319 missense mutations were identified solely in the proline domain from human cancers. Six hotspot mutations were identified at amino acids 72, 73, 82, 84, 89, and 98. Codon 72 contains a polymorphism that changes from proline (and African descent) to arginine (with
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PRMT4 promotes ferroptosis to aggravate doxorubicin-induced cardiomyopathy via inhibition of the Nrf2/GPX4 pathway Cell Death Differ. (IF 8.086) Pub Date : 2022-04-05 Yilong Wang, Shu Yan, Xuemei Liu, Fei Deng, Pengchao Wang, Liuye Yang, Lizhi Hu, Kai Huang, Jiangui He
Doxorubicin (DOX), a commonly used antitumor agent, is often accompanied by its dosage-dependent cardiotoxicity, which incorporates ferroptosis in its pathogenesis. Protein arginine methyltransferase 4 (PRMT4) is a transcription regulator involved in the modulation of oxidative stress and autophagy, but its role in DOX-induced cardiomyopathy (DIC) and ferroptosis remains elusive. Herein, we aimed to
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Exploring the future of research in the Tp53 field. Cell Death Differ. (IF 8.086) Pub Date : 2022-04-05 Arnold J Levine
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Disease-associated KBTBD4 mutations in medulloblastoma elicit neomorphic ubiquitylation activity to promote CoREST degradation Cell Death Differ. (IF 8.086) Pub Date : 2022-04-04 Zhuoyao Chen, Rafael M. Ioris, Stacey Richardson, Ava N. Van Ess, Iolanda Vendrell, Benedikt M. Kessler, Francesca M. Buffa, Luca Busino, Steven C. Clifford, Alex N. Bullock, Vincenzo D’Angiolella
Medulloblastoma is the most common malignant brain tumour in children. Genomic studies have identified distinct disease subgroups: wnt/wingless (WNT), sonic hedgehog (SHH), and non-WNT/non-SHH, comprising group 3 and group 4. Alterations in WNT and SHH signalling form the pathogenetic basis for their subgroups, whereas those for non-WNT/non-SHH tumours remain largely elusive. Recent analyses have revealed
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Mutant p53: it’s not all one and the same Cell Death Differ. (IF 8.086) Pub Date : 2022-03-31 Margaret C. Kennedy, Scott W. Lowe
Mutation of the TP53 tumor suppressor gene is the most common genetic alteration in cancer, and almost 1000 alleles have been identified in human tumors. While virtually all TP53 mutations are thought to compromise wild type p53 activity, the prevalence and recurrence of missense TP53 alleles has motivated countless research studies aimed at understanding the function of the resulting mutant p53 protein
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Loss of TAF8 causes TFIID dysfunction and p53-mediated apoptotic neuronal cell death Cell Death Differ. (IF 8.086) Pub Date : 2022-03-31 Farrah El-Saafin, Maria I. Bergamasco, Yunshun Chen, Rose E. May, Prabagaran Esakky, Soroor Hediyeh-zadeh, Mathew Dixon, Stephen Wilcox, Melissa J. Davis, Andreas Strasser, Gordon K. Smyth, Tim Thomas, Anne K. Voss
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Cell cycle regulation: p53-p21-RB signaling Cell Death Differ. (IF 8.086) Pub Date : 2022-03-31 Kurt Engeland
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The TP53 Database: transition from the International Agency for Research on Cancer to the US National Cancer Institute. Cell Death Differ. (IF 8.086) Pub Date : 2022-03-29 Kelvin César de Andrade,Elaine E Lee,Elise M Tookmanian,Chimene A Kesserwan,James J Manfredi,Jessica N Hatton,Jennifer K Loukissas,Jiri Zavadil,Lei Zhou,Magali Olivier,Megan N Frone,Owais Shahzada,William J R Longabaugh,Christian P Kratz,David Malkin,Pierre Hainaut,Sharon A Savage
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Inhibition of cGAS-STING by JQ1 alleviates oxidative stress-induced retina inflammation and degeneration Cell Death Differ. (IF 8.086) Pub Date : 2022-03-28 Ming Zou, Qin Ke, Qian Nie, Ruili Qi, Xingfei Zhu, Wei Liu, Xuebin Hu, Qian Sun, Jia-Ling Fu, Xiangcheng Tang, Yizhi Liu, David Wan-Cheng Li, Lili Gong
Atrophic (“dry”) form of age-related macular degeneration (AMD) is a leading cause of vision loss characterized by macular retinal pigment epithelium (RPE) and the ensuing photoreceptor degeneration. cGAS-STING signaling is a key cytosolic DNA sensor system in innate immunity and have recently been shown promotes RPE degeneration. However, expression regulation and therapeutic potential of cGAS and
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BAX and BAK dynamics control mitochondrial DNA release during apoptosis Cell Death Differ. (IF 8.086) Pub Date : 2022-03-26 Takahiro Yamazaki, Lorenzo Galluzzi
BAX and BAK are generally considered as fully interchangeable for mitochondrial permeabilization and consequent apoptotic cell death. Garcia-Saez and colleagues have recently documented striking kinetic differences that influence BAX and BAK oligomerization at the mitochondrial surface. These data have important implications for inflammatory responses driven by mitochondrial DNA.
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Regulation of Semaphorin3A in the process of cutaneous wound healing Cell Death Differ. (IF 8.086) Pub Date : 2022-03-26 Yang Zheng, Feng Jiang, Chao Wang, Mengjie Dong, Chundi Wang, Enshi Yan, Yi Wang, Zaiou Zhu, Xianbin Xiong, Xu Ding, Jinhai Ye, Yue He, Hongchuang Zhang, Junbo Zhou, Wei Zhang, Yunong Wu, Xiaomeng Song
Semaphorin 3A (Sema3A) has been recognized as a crucial regulator of morphogenesis and homeostasis over a wide range of organ systems. However, its function in cutaneous wound healing is poorly understood. In our study, we demonstrated that Sema3A adenovirus plasmids transfection limited keratinocyte proliferation and decreased migrative capacity as assessed by in vitro wound healing assay. Sema3A
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Long noncoding RNA NEAT1 promotes ferroptosis by modulating the miR-362-3p/MIOX axis as a ceRNA Cell Death Differ. (IF 8.086) Pub Date : 2022-03-25 Ying Zhang, Meiying Luo, Xiaohong Cui, Douglas O’Connell, Yongfei Yang
Ferroptosis, a novel form of regulated cell death induced by iron-dependent lipid peroxidation, plays an essential role in the development and drug resistance of tumors. Long noncoding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) has been reported to be involved in the regulation of cell cycle, proliferation, apoptosis, and migration of tumor cells. However, the function and molecular
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BH3 mimetic drugs cooperate with Temozolomide, JQ1 and inducers of ferroptosis in killing glioblastoma multiforme cells Cell Death Differ. (IF 8.086) Pub Date : 2022-03-24 Diane Moujalled, Adam G. Southon, Eiman Saleh, Kerstin Brinkmann, Francine Ke, Melinda Iliopoulos, Ryan S. Cross, Misty R. Jenkins, Duong Nhu, Zilu Wang, Melissa X. Shi, Ruth M. Kluck, Guillaume Lessene, Stephanie Grabow, Ashley I. Bush, Andreas Strasser
Glioblastoma multiforme (GBM) is the most common and aggressive form of brain cancer, with treatment options often constrained due to inherent resistance of malignant cells to conventional therapy. We investigated the impact of triggering programmed cell death (PCD) by using BH3 mimetic drugs in human GBM cell lines. We demonstrate that co-targeting the pro-survival proteins BCL-XL and MCL-1 was more
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Activation of Drp1 promotes fatty acids-induced metabolic reprograming to potentiate Wnt signaling in colon cancer Cell Death Differ. (IF 8.086) Pub Date : 2022-03-24 Xiaopeng Xiong, Sumati Hasani, Lyndsay E. A. Young, Dylan R. Rivas, Ashley T. Skaggs, Rebecca Martinez, Chi Wang, Heidi L. Weiss, Matthew S. Gentry, Ramon C. Sun, Tianyan Gao
Cancer cells are known for their ability to adapt variable metabolic programs depending on the availability of specific nutrients. Our previous studies have shown that uptake of fatty acids alters cellular metabolic pathways in colon cancer cells to favor fatty acid oxidation. Here, we show that fatty acids activate Drp1 to promote metabolic plasticity in cancer cells. Uptake of fatty acids (FAs) induces
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Should mutant TP53 be targeted for cancer therapy? Cell Death Differ. (IF 8.086) Pub Date : 2022-03-24 Zilu Wang, Andreas Strasser, Gemma L. Kelly
Mutations in the TP53 tumour suppressor gene are found in ~50% of human cancers [1,2,3,4,5,6]. TP53 functions as a transcription factor that directly regulates the expression of ~500 genes, some of them involved in cell cycle arrest/cell senescence, apoptotic cell death or DNA damage repair, i.e. the cellular responses that together prevent tumorigenesis [1,2,3,4,5,6]. Defects in TP53 function not
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Disruption of GMNC-MCIDAS multiciliogenesis program is critical in choroid plexus carcinoma development Cell Death Differ. (IF 8.086) Pub Date : 2022-03-23 Qun Li, Zhiyuan Han, Navleen Singh, Berta Terré, Ryann M. Fame, Uzayr Arif, Thomas D. Page, Tasneem Zahran, Ahmed Abdeltawab, Yuan Huang, Ping Cao, Jun Wang, Hao Lu, Hart G. W. Lidov, Kameswaran Surendran, Lizhao Wu, James Q. Virga, Ying-Tao Zhao, Ulrich Schüller, Robert J. Wechsler-Reya, Maria K. Lehtinen, Sudipto Roy, Zhongmin Liu, Travis H. Stracker, Haotian Zhao
Multiciliated cells (MCCs) in the brain reside in the ependyma and the choroid plexus (CP) epithelia. The CP secretes cerebrospinal fluid that circulates within the ventricular system, driven by ependymal cilia movement. Tumors of the CP are rare primary brain neoplasms mostly found in children. CP tumors exist in three forms: CP papilloma (CPP), atypical CPP, and CP carcinoma (CPC). Though CPP and