Explanipedia

Enteropathogenic bacteria evade ROCK-driven epithelial cell extrusion Open

Giovanni Luchetti, Marin Miner, R. Peterson, W. P. Scott, Praveen Krishnamoorthy , et al. · 2025

Diverse pathogen-encoded virulence factors disable apoptosis, pyroptosis or necroptosis, the host cell death programs that remove infected cells¹. In the intestine, the extrusion of infected cells into the lumen for elimination …

IRF2 degradation tunes the innate immune response Open

Cristhian Cadena, Rohit Reja, Emma Bolech, Joshua D. Webster, Vasumathi Kameswaran , et al. · 2025

Summary The transcription factor IRF2 protects against skin inflammation in mice and humans but, paradoxically, promotes pyroptosis by inducing Gsdmd . How IRF2 activates some proinflammatory genes, but suppresses others is unclear. We sho…

COP1 Deficiency in BRAFV600E Melanomas Confers Resistance to Inhibitors of the MAPK Pathway Open

Ada Ndoja, Christopher M. Rose, Eva Lin, Rohit Reja, Jelena Petrovic , et al. · 2025

Aberrant activation of the mitogen-activated protein kinase (MAPK) cascade promotes oncogenic transcriptomes. Despite efforts to inhibit oncogenic kinases, such as BRAFV600E, tumor responses in patients can be heterogeneous and limited by …

Impairment of DET1 causes neurological defects and lethality in mice and humans Open

Özge Karayel, Allison Soung, Hem R. Gurung, Alexander F. Schubert, Susan Klaeger , et al. · 2025

COP1 and DET1 are components of an E3 ubiquitin ligase that is conserved from plants to humans. Mammalian COP1 binds to DET1 and is a substrate adaptor for the CUL4A-DDB1-RBX1 RING E3 ligase. Transcription factor substrates, including c-Ju…

Autoinhibition of dimeric NINJ1 prevents plasma membrane rupture Open

Sergei Pourmal, Melissa E. Truong, Matthew C. Johnson, Ying Yang, Lijuan Zhou , et al. · 2024

N4BP1 coordinates ubiquitin-dependent crosstalk within the IκB kinase family to limit Toll-like receptor signaling and inflammation Open

Alexander D. Gitlin, Allie Maltzman, Yuzuka Kanno, Klaus Heger, Rohit Reja , et al. · 2024

ZBP1 and TRIF trigger lethal necroptosis in mice lacking caspase-8 and TNFR1 Open

Margaret Solon, Nianfeng Ge, Shannon Hambro, Susan Haller, Jian Jiang , et al. · 2024

Necroptosis is a lytic form of cell death that is mediated by the kinase RIPK3 and the pseudokinase MLKL when caspase-8 is inhibited downstream of death receptors, toll-like receptor 3 (TLR3), TLR4, and the intracellular Z-form nucleic aci…

Caspase cleavage of RIPK3 after Asp333 is dispensable for mouse embryogenesis Open

Kim Newton, Katherine E. Wickliffe, Allie Maltzman, Debra L. Dugger, Joshua D. Webster , et al. · 2024

The proteolytic activity of caspase-8 suppresses lethal RIPK1-, RIPK3- and MLKL-dependent necroptosis during mouse embryogenesis. Caspase-8 is reported to cleave RIPK3 in addition to the RIPK3-interacting kinase RIPK1, but whether cleavage…

Cell death Open

Kim Newton, Andreas Strasser, Nobuhiko Kayagaki, Vishva M. Dixit · 2024

Control of Cell Death in Health and Disease Open

Nobuhiko Kayagaki, Joshua D. Webster, Kim Newton · 2023

Apoptosis, necroptosis, and pyroptosis are genetically programmed cell death mechanisms that eliminate obsolete, damaged, infected, and self-reactive cells. Apoptosis fragments cells in a manner that limits immune cell activation, whereas …

Targeted alveolar regeneration with Frizzled-specific agonists Open

Ahmad N. Nabhan, Joshua D. Webster, Jarrett Adams, Levi L. Blazer, Christine Everrett , et al. · 2023

Inhibiting membrane rupture with NINJ1 antibodies limits tissue injury Open

Nobuhiko Kayagaki, Irma B. Stowe, Kamela Alegre, Ishan Deshpande, Shuang Wu , et al. · 2023

Plasma membrane rupture (PMR) in dying cells undergoing pyroptosis or apoptosis requires the cell-surface protein NINJ1 1 . PMR releases pro-inflammatory cytoplasmic molecules, collectively called damage-associated molecular patterns (DAMP…

XIAP deletion sensitizes mice to TNF-induced and RIP1-mediated death Open

Axel Witt, Tatiana Goncharov, Yujung Michelle Lee, Matthias Kist, Monika Dohse , et al. · 2023

Deubiquitinases in cell death and inflammation Open

Kim Newton, Alexander D. Gitlin · 2022

Apoptosis, pyroptosis, and necroptosis are distinct forms of programmed cell death that eliminate infected, damaged, or obsolete cells. Many proteins that regulate or are a part of the cell death machinery undergo ubiquitination, a post-tr…

Healthcare workers benefit from second dose of COVID-19 mRNA vaccine: Effects of partial and full vaccination on sick leave duration and symptoms Open

Earl Strum, Yolee Casagrande, Kim Newton, Jennifer B. Unger · 2022

COVID-19 vaccination has the potential to prevent long absences from work and the adverse financial, staffing, and managerial consequences of these long absences.

Healthcare workers benefit from second dose of COVID-19 mRNA vaccine: Effects of partial and full vaccination on sick leave duration and symptoms Open

Earl Strum, Yolee Casagrande, Kim Newton, Jennifer B. Unger · 2021

Importance In addition to morbidity and mortality of individuals, COVID-19 can affect staffing among organizations. It is important to determine whether vaccination can mitigate this burden. Objective : This study examined the association …

Shigella ubiquitin ligase IpaH7.8 targets gasdermin D for degradation to prevent pyroptosis and enable infection Open

Giovanni Luchetti, Justin L. Roncaioli, Roberto A. Chavez, Alexander F. Schubert, Eric M. Kofoed , et al. · 2021

Selective activation of PFKL suppresses the phagocytic oxidative burst Open

Neri Amara, Madison P. Cooper, Maria A. Voronkova, Bradley A. Webb, Eric M. Lynch , et al. · 2021

In neutrophils, nicotinamide adenine dinucleotide phosphate (NADPH) generated via the pentose phosphate pathway fuels NADPH oxidase NOX2 to produce reactive oxygen species for killing invading pathogens. However, excessive NOX2 activity ca…

Impaired RIPK1 ubiquitination sensitizes mice to TNF toxicity and inflammatory cell death Open

Matthias Kist, László G. Kömüves, Tatiana Goncharov, Debra L. Dugger, Charles Q. Yu , et al. · 2020

Receptor-interacting protein 1 (RIP1; RIPK1) is a key regulator of multiple signaling pathways that mediate inflammatory responses and cell death. TNF-TNFR1 triggered signaling complex formation, subsequent NF-κB and MAPK activation and in…

Ubiquitin Ligase COP1 Suppresses Neuroinflammation by Degrading c/EBPβ in Microglia Open

Ada Ndoja, Rohit Reja, Seung-Hye Lee, Joshua D. Webster, Hai Ngu , et al. · 2020

Multitasking Kinase RIPK1 Regulates Cell Death and Inflammation Open

Kim Newton · 2019

Receptor-interacting serine threonine kinase 1 (RIPK1) is a widely expressed kinase that is essential for limiting inflammation in both mice and humans. Mice lacking RIPK1 die at birth from multiorgan inflammation and aberrant cell death, …

Autophagy regulates inflammatory programmed cell death via turnover of RHIM-domain proteins Open

Junghyun Lim, Hyunjoo Park, Jason Heisler, Timurs Maculins, Merone Roose‐Girma , et al. · 2019

RIPK1, RIPK3, ZBP1 and TRIF, the four mammalian proteins harboring RIP homotypic interaction motif (RHIM) domains, are key components of inflammatory signaling and programmed cell death. RHIM-domain protein activation is mediated by their …

Author response: Autophagy regulates inflammatory programmed cell death via turnover of RHIM-domain proteins Open

Junghyun Lim, Hyunjoo Park, Jason Heisler, Timurs Maculins, Merone Roose‐Girma , et al. · 2019

RIP1 inhibition blocks inflammatory diseases but not tumor growth or metastases Open

Snahel Patel, Joshua D. Webster, Eugene Varfolomeev, Youngsu Kwon, Jason Cheng , et al. · 2019

Ubiquitin Ligases cIAP1 and cIAP2 Limit Cell Death to Prevent Inflammation Open

Jieqiong Zhang, Joshua D. Webster, Debra L. Dugger, Tatiana Goncharov, Merone Roose‐Girma , et al. · 2019

Cellular inhibitor of apoptosis proteins cIAP1 and cIAP2 ubiquitinate nuclear factor κB (NF-κB)-inducing kinase (NIK) to suppress non-canonical NF-κB signaling and substrates such as receptor interacting protein kinase 1 (RIPK1) to promote…

The Gag protein PEG10 binds to RNA and regulates trophoblast stem cell lineage specification Open

Mona Abed, Erik Verschueren, Hanna G. Budayeva, Peter Liu, Donald S. Kirkpatrick , et al. · 2019

Peg10 (paternally expressed gene 10) is an imprinted gene that is essential for placental development. It is thought to derive from a Ty3-gyspy LTR (long terminal repeat) retrotransposon and retains Gag and Pol-like domains. Here we show t…

The Gag Protein PEG10 Binds to RNA and Regulates Trophoblast Stem Cell Lineage Specification Open

Mona Abed, Erik Verschueren, Hanna G. Budayeva, Peter Liu, Donald S. Kirkpatrick , et al. · 2019

Peg10 (paternally expressed gene 10) is an imprinted gene that is essential for placental development. It is thought to derive from a Ty3-gyspy LTR (long terminal repeat) retrotransposon and retains Gag and Pol-like domains. Here we show t…

Ubiquitin ligase COP1 coordinates transcriptional programs that control cell type specification in the developing mouse brain Open

Kim Newton, Debra L. Dugger, Arundhati Sengupta-Ghosh, Ronald E. Ferrando, Felix Chu , et al. · 2018

Significance The ubiquitin ligase CRL4 COP1/DET1 modifies specific transcription factor substrates with polyubiquitin so that they are degraded. However, the Ras–MEK–ERK signaling pathway can inactivate CRL4 COP1/DET1 and thereby promote t…

Faculty Opinions recommendation of LUBAC is essential for embryogenesis by preventing cell death and enabling haematopoiesis. Open

Vishva M. Dixit, Kim Newton · 2018

The Linear Ubiquitin chain Assembly Complex (LUBAC) is required for optimal gene activation and prevention of cell death upon activation of immune receptors, including TNFR11.Deficiency in the LUBAC components SHARPIN or HOIP in mice resul…

CRISPR whole-genome screening identifies new necroptosis regulators and RIPK1 alternative splicing Open

Marinella Callow, Colin Watanabe, Katherine E. Wickliffe, Russell Bainer, Sarah Kummerfield , et al. · 2018

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