Publication
Title
Intermediate domain of receptor-interacting protein Kinase 1 (RIPK1) determines switch between necroptosis and RIPK1 Kinase-dependent apoptosis
Author
Abstract
Receptor-interacting protein kinase 1 (RIPK1) is an important component of the tumor necrosis factor receptor 1 (TNFR1) signaling pathway. Depending on the cell type and conditions, RIPK1 mediates MAPK and NF-kappa B activation as well as cell death. Using a mutant form of RIPK1 (RIPK1 Delta ID) lacking the intermediate domain (ID), we confirm the requirement of this domain for activation of these signaling events. Moreover, expression of RIPK1 Delta ID resulted in enhanced recruitment of caspase-8 to the TNFR1 complex II component Fas-associated death domain (FADD), which allowed a shift from TNF-induced necroptosis to apoptosis in L929 cells. Addition of the RIPK1 kinase inhibitor necrostatin-1 strongly reduced recruitment of RIPK1 and caspase-8 to FADD and subsequent apoptosis, indicating a role for RIPK1 kinase activity in apoptotic complex formation. Our study shows that RIPK1 has an anti-apoptotic function residing in its ID and demonstrates a cellular system as an elegant genetic model for RIPK1 kinase-dependent apoptosis that, in contrast to the Smac mimetic model, does not rely on depletion of cellular inhibitor of apoptosis protein 1 and 2 (cIAP1/2).
Language
English
Source (journal)
Journal of biological chemistry. - Baltimore, Md
Publication
Baltimore, Md : 2012
ISSN
0021-9258 [print]
1083-351X [online]
Volume/pages
287 :18 (2012) , p. 14863-14872
ISI
000304003200050
Full text (Publisher's DOI)
UAntwerpen
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 18.10.2018
Last edited 30.10.2021