More to Life than NF-κB in TNFR1 Signaling.

Abstract:

:TNF is a master proinflammatory cytokine whose pathogenic role in inflammatory disorders has long been attributed to induction of proinflammatory mediators. TNF also activates cell survival and death pathways, and recent studies demonstrated that TNF also causes inflammation by inducing cell death. The default response of most cells to TNF is survival and NF-κB-mediated upregulation of prosurvival molecules is a well-documented protective mechanism downstream of TNFR1. Recent studies revealed the existence of an NF-κB-independent cell death checkpoint that restricts cell demise by inactivating RIPK1. Disruption of this checkpoint leads to RIPK1 kinase-dependent death and causes inflammation in vivo. These revelations bring complexity to the control of TNF-induced cell death, and suggest clinical benefit of RIPK1 inhibitors in TNF-driven human inflammatory disorders.

journal_name

Trends Immunol

journal_title

Trends in immunology

authors

Ting AT,Bertrand MJM

doi

10.1016/j.it.2016.06.002

subject

Has Abstract

pub_date

2016-08-01 00:00:00

pages

535-545

issue

8

eissn

1471-4906

issn

1471-4981

pii

S1471-4906(16)30057-6

journal_volume

37

pub_type

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