RIP3: a molecular switch for necrosis and inflammation.
TLDR
The current understanding of the mechanisms that drive RIP3-dependent necrosis and its role in different inflammatory diseases is reviewed.Abstract:
The receptor-interacting protein kinase 3 (RIP3/RIPK3) has emerged as a critical regulator of programmed necrosis/ necroptosis, an inflammatory form of cell death with important functions in pathogen-induced and sterile inflammation. RIP3 activation is tightly regulated by phosphorylation, ubiquitination, and caspase-mediated cleavage. These post-translational modifications coordinately regulate the assembly of a macromolecular signaling complex termed the necrosome. Recently, several reports indicate that RIP3 can promote inflammation independent of its pronecrotic activity. Here, we review our current understanding of the mechanisms that drive RIP3-dependent necrosis and its role in different inflammatory diseases.read more
Citations
More filters
Journal ArticleDOI
NLRP3 inflammasome activation and cell death.
Yi Huang,Wen Xu,Rongbin Zhou +2 more
TL;DR: In this paper, the authors summarize the inextricable link between NLRP3 inflammasome activation and cell death and discuss potential therapeutics that target cell death effectors in NLRP-associated diseases.
Journal ArticleDOI
The Pathogen Candida albicans Hijacks Pyroptosis for Escape from Macrophages
Nathalie Uwamahoro,Jiyoti Verma-Gaur,Hsin-Hui Shen,Yue Qu,Rowena S. Lewis,Rowena S. Lewis,Jingxiong Lu,Keith R. Bambery,Seth L. Masters,Seth L. Masters,James E Vince,James E Vince,Thomas Naderer,Ana Traven +13 more
TL;DR: The data provide a new model for how the interplay between fungal morphogenesis and activation of a host cell death pathway mediates macrophage killing by C. albicans hyphae and suggest that the defects of the Mediator mutants in causing macrophages death are caused, at least in part, by reduced activation of pyroptosis.
Journal ArticleDOI
Molecular mechanisms of regulated necrosis
TL;DR: The signaling pathways, pathophysiological relevance and therapeutic implications of the major molecular cascades that underlie RN are reviewed, highlighting the degree of interconnectivity that characterizes RN.
Journal ArticleDOI
The B-RafV600E inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury
Jianxin Li,Jian-Ming Feng,Yingxia Wang,Xuxia Li,Xing Chen,Yang Su,Yan Yan Shen,Yanhong Chen,Bing Xiong,Chen Yang,Jian Ding,Ze-Hong Miao +11 more
TL;DR: The results indicate that the anticancer B-RafV600E inhibitor dabrafenib is a RIP3 inhibitor, which could serve as a sharp tool for probing the RIP3 biology and as a potential preventive or therapeutic agent for RIP3-involved necroptosis-related diseases such as acetaminophen-induced liver damage.
Journal ArticleDOI
SARS-Coronavirus Open Reading Frame-3a drives multimodal necrotic cell death.
Yuan Yue,Neel R. Nabar,Chong-Shan Shi,Olena Kamenyeva,Xun Xiao,Xun Xiao,Il-Young Hwang,Min Wang,John H. Kehrl +8 more
TL;DR: Rip3-mediated oligomerization of Sars 3a causes necrotic cell death, lysosomal damage, and caspase-1 activation—all likely contributing to the clinical manifestations of SARS-CoV infection.
References
More filters
Journal ArticleDOI
Hallmarks of cancer: the next generation.
TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
Journal ArticleDOI
Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.
TL;DR: Apoptosis seems to be involved in cell turnover in many healthy adult tissues and is responsible for focal elimination of cells during normal embryonic development, and participates in at least some types of therapeutically induced tumour regression.
Journal ArticleDOI
Cancer-related inflammation.
TL;DR: The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.
Journal ArticleDOI
An endotoxin-induced serum factor that causes necrosis of tumors
TL;DR: It is proposed that TNF mediates endotoxin-induced tumor necrosis, and that it may be responsible for the suppression of transformed cells by activated macrophages.
Journal ArticleDOI
Proapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death
Michael C. Wei,Michael C. Wei,Wei-Xing Zong,Emily H. Cheng,Tullia Lindsten,Vily Panoutsakopoulou,Andrea J. Ross,Kevin A. Roth,Grant R. MacGregor,Craig B. Thompson,Stanley J. Korsmeyer +10 more
TL;DR: In this article, the authors found that doubly deficient cells are resistant to multiple apoptotic stimuli that act through disruption of mitochondrial function: staurosporine, ultraviolet radiation, growth factor deprivation, etoposide, and the endoplasmic reticulum stress stimuli thapsigargin and tunicamycin.