Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

TRIM21, a new component of the TRAIL-induced endogenous necrosome complex

Eugénio, Mélanie Simoes, Faurez, Florence, Kara-Ali, Ghania H., Lagarrigue, Mélanie, Uhart, Perrine, Bonnet, Marion C., Gallais, Isabelle, Com, Emmanuelle, Pineau, Charles, Samson, Michel, Le Seyec, Jacques and Diamanche-Boitrel, Marie-Thérèse 2021. TRIM21, a new component of the TRAIL-induced endogenous necrosome complex. Frontiers in Molecular Biosciences 8 , 645134. 10.3389/fmolb.2021.645134

[thumbnail of Simoes-Eugenio et al. 2021 fmolb-08-645134.pdf]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a well-known apoptosis inducer and a potential anticancer agent. When caspases and inhibitors of apoptosis proteins (IAPs) are inhibited, TRAIL induces necroptosis. Molecular mechanisms of necroptosis rely on kinase activation, and on the formation of a necrosome complex, bringing together the receptor-interacting protein kinases 1 and 3 (RIPK1, RIPK3), and the mixed lineage kinase domain-like protein (MLKL). In this study, mass spectrometry approach allowed to identify the tripartite motif containing 21 (TRIM21), an E3 ubiquitin-protein ligase as a new partner of the endogenous TRAIL-induced necrosome. Alteration of TRIM21 expression level, obtained by transient transfection of HT29 or HaCat cells with TRIM21-targeted siRNAs or cDNA plasmids coding for TRIM21 demonstrated that TRIM21 is a positive regulator of TRAIL-induced necroptosis. Furthermore, the invalidation of TRIM21 expression in HT29 cells by CRISPR-Cas9 technology also decreased cell sensitivity to TRAIL-induced necroptosis, a shortcoming associated with a reduction in MLKL phosphorylation, the necroptosis executioner. Thus, TRIM21 emerged as a new partner of the TRAIL-induced necrosome that positively regulates the necroptosis process.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Frontiers Media
ISSN: 2296-889X
Date of First Compliant Deposit: 15 April 2021
Date of Acceptance: 17 February 2021
Last Modified: 16 Apr 2021 14:00
URI: https://orca.cardiff.ac.uk/id/eprint/140497

Citation Data

Cited 1 time in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics