Receptor interacting protein 1 (RIP1) kinase is a critical regulator of inflammation and cell death signaling, and plays a crucial role in maintaining immune responses and proper tissue homeostasis. Mounting evidence argues for the importance of RIP1 post-translational modifications in control of its function. Ubiquitination by E3 ligases, such as inhibitors of apoptosis (IAP) proteins and LUBAC, as well as the reversal of these modifications by deubiquitinating enzymes, such as A20 and CYLD, can greatly influence RIP1 mediated signaling. In addition, cleavage by caspase-8, RIP1 autophosphorylation, and phosphorylation by a number of signaling kinases can greatly impact cellular fate. Disruption of the tightly regulated RIP1 modifications can lead to signaling disbalance in TNF and/or TLR controlled and other inflammatory pathways, and result in severe human pathologies. This review will focus on RIP1 and its many modifications with an emphasis on ubiquitination, phosphorylation, and cleavage, and their functional impact on the RIP1's role in signaling pathways.
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May 2022
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Cover Image
Cover Image
Immunofluorescence staining of TP1 in seminiferous tubules from RimklbIII +/+ and Rim k lb/mice. Nuclei were stained with DAPI and the acrosome with PNA lectin. TP1 was present in seminiferous stages II in both genotypes. TP1 was undetectable at stage VII bars, 50 µm. Image from Eckhardt and colleagues (pp. 953–972).
Review Article|
May 06 2022
RIP1 post-translational modifications
In Collection
Cell death and survival
Eugene Varfolomeev;
Eugene Varfolomeev
Department of Early Discovery Biochemistry, Genentech, South San Francisco, CA 94110, U.S.A.
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Domagoj Vucic
Department of Early Discovery Biochemistry, Genentech, South San Francisco, CA 94110, U.S.A.
Correspondence: Domagoj Vucic (domagoj@gene.com)
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Publisher: Portland Press Ltd
Received:
February 19 2022
Revision Received:
April 13 2022
Accepted:
April 19 2022
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2022
Biochem J (2022) 479 (9): 929–951.
Article history
Received:
February 19 2022
Revision Received:
April 13 2022
Accepted:
April 19 2022
Citation
Eugene Varfolomeev, Domagoj Vucic; RIP1 post-translational modifications. Biochem J 13 May 2022; 479 (9): 929–951. doi: https://doi.org/10.1042/BCJ20210725
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