X-linked Inhibitor of Apoptosis-associated Factor 1 Regulates TNF Receptor 1 Complex Stability

Overview

Journal FEBS Lett

Specialty Biochemistry

Date 2016 Nov 4

PMID 27768232

Citations 2

Authors

Boren Lin

Da Xu

Douglas W Leaman

Affiliations

Soon will be listed here.

Abstract

X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a cytokine-regulated, tumor necrosis factor (TNF) receptor-associated factor (TRAF) domain-containing protein that has a poorly defined cellular function. Here, we show that ectopically expressed XAF1 inhibits TNF-ɑ-induced NF-κB activation, whereas shRNA silencing of endogenous XAF1 augments it. Our data suggest that XAF1 may inhibit TNF-ɑ-induced NF-κB activation by disrupting the assembly of the TRADD/TRAF2/RIP1 complex (complex I) downstream of TNF receptor activation. XAF1 interacts with TRAF2 and inhibits TRAF2-dependent NF-κB activation, in part, by blocking TRAF2 polyubiquitination. Our findings also indicate that although XAF1 does not directly inhibit RIP1-dependent NF-κB activation, it binds RIP1 and disrupts RIP1/TRADD association. Our data suggest that XAF1 acts as a feedback regulator of the TNF receptor signaling pathway to suppress NF-κB activation.

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