UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Phosphorylation of RIPK1 serine 25 mediates IKK dependent control of extrinsic cell death in T cells

Blanchett, Sam; Dondelinger, Yves; Barbarulo, Alessandro; Bertrand, Mathieu JM; Seddon, Benedict; (2022) Phosphorylation of RIPK1 serine 25 mediates IKK dependent control of extrinsic cell death in T cells. Frontiers in Immunology , 13 , Article 1067164. 10.3389/fimmu.2022.1067164. Green open access

[thumbnail of fimmu-13-1067164.pdf]
Preview
Text
fimmu-13-1067164.pdf - Published Version

Download (10MB) | Preview

Abstract

The Inhibitor of Kappa B Kinase (IKK) complex is a critical regulator of NF-κB activation. More recently, IKK has also been shown to repress RIPK1 dependent extrinsic cell death pathways by directly phosphorylating RIPK1 at serine 25. In T cells, IKK expression is essential for normal development in the thymus, by promoting survival of thymocytes independently of NF-κB activation. RIPK1 undergoes extensive phosphorylation following TNF stimulation in T cells, though which targets are required to repress RIPK1 has not been defined. Here, we show that TNF induced phosphorylation of RIPK1 at S25 is IKK dependent. We test the relevance of this phosphorylation event in T cells using mice with a RIPK1S25D phosphomimetic point mutation to endogenous RIPK1. We find that this mutation protects T cells from TNF induced cell death when IKK activity is inhibited in vitro, and can rescues development of IKK deficient thymocytes in vivo to a degree comparable with kinase dead RIPK1D138N. Together, these data show that phosphorylation of RIPK1S25 by IKK represents a key regulatory event promoting survival of T cells by IKK.

Type: Article
Title: Phosphorylation of RIPK1 serine 25 mediates IKK dependent control of extrinsic cell death in T cells
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2022.1067164
Publisher version: https://doi.org/10.3389/fimmu.2022.1067164
Language: English
Additional information: © 2022 Blanchett, Dondelinger, Barbarulo, Bertrand and Seddon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: T cells, extrinsic cell death, RIPK1, IKK complex, TNF
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10162366
Downloads since deposit
25Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item