Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1042/BCJ20210725 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Protein shapeshifting in necroptotic cell death signaling.
Trends Biochem Sci
February 2025
Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, A
Necroptosis is a mode of programmed cell death executed by the mixed lineage kinase domain-like (MLKL) pseudokinase following its activation by the upstream receptor-interacting protein kinase-3 (RIPK3), subsequent to activation of death, Toll-like, and pathogen receptors. The pathway originates in innate immunity, although interest has surged in therapeutically targeting necroptosis owing to its dysregulation in inflammatory diseases. Here, we explore how protein conformation and higher order assembly of the pathway effectors - Z-DNA-binding protein-1 (ZBP1), RIPK1, RIPK3, and MLKL - can be modulated by post-translational modifications, such as phosphorylation, ubiquitylation, and lipidation, and intermolecular interactions to tune activities and modulate necroptotic signaling flux.
View Article and Find Full Text PDFSpermidine mediates acetylhypusination of RIPK1 to suppress diabetes onset and progression.
Nat Cell Biol
December 2024
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
It has been established that N-acetyltransferase (murine NAT1 (mNAT1) and human NAT2 (hNAT2)) mediates insulin sensitivity in type 2 diabetes. Here we show that mNAT1 deficiency leads to a decrease in cellular spermidine-a natural polyamine exhibiting health-protective and anti-ageing effects-but understanding of its mechanism is limited. We identify that mNAT1 and hNAT2 modulate a type of post-translational modification involving acetylated spermidine, which we name acetylhypusination, on receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-a key regulator of inflammation and cell death.
View Article and Find Full Text PDFRoles of RIPK1 as a stress sentinel coordinating cell survival and immunogenic cell death.
Nat Rev Mol Cell Biol
November 2023
The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, London, UK.
Cell death and inflammation are closely linked arms of the innate immune response to combat infection and tissue malfunction. Recent advancements in our understanding of the intricate signals originating from dying cells have revealed that cell death serves as more than just an end point. It facilitates the exchange of information between the dying cell and cells of the tissue microenvironment, particularly immune cells, alerting and recruiting them to the site of disturbance.
View Article and Find Full Text PDFRIP1 post-translational modifications.
Biochem J
May 2022
Department of Early Discovery Biochemistry, Genentech, South San Francisco, CA 94110, U.S.A.
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.
View Article and Find Full Text PDFThe latest information on the RIPK1 post-translational modifications and functions.
Biomed Pharmacother
October 2021
Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing 100029, China; Department of Emergency, China-Japan Friendship Hospital, Beijing 100029, China. Electronic address:
RIPK1 is a protein kinase that simultaneously regulates inflammation, apoptosis, and necroptosis. It is thought that RIPK1 has separate functions through its scaffold structure and kinase domains. Moreover, different post-translational modifications in RIPK1 play distinct or even opposing roles.
View Article and Find Full Text PDF