ANKRD13a Controls Early Cell-death Checkpoint by Interacting with RIP1 Independent of NF-κB

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2021 Nov 28

PMID 34839354

Citations 5

Authors

Minho Won

Kyeong Ah Park

Sup Kim

Eunjin Ju

Youngbok Ko

Heonjong Yoo

Hyunju Ro

Jaeseob Lee

Junseo Oh

Eun Gyo Lee

Sang Yean Kim

Suk Woo Nam

Han-Ming Shen

Min-Kyung Yeo

Jin Man Kim

Gang Min Hur

Affiliations

Soon will be listed here.

Abstract

In TNF signaling, ubiquitination of RIP1 functions as an early cell-death checkpoint, which prevents the spatial transition of the signaling complex from complex-I to death-inducing complex-II. Here, we report that ankyrin repeat domain 13a (ANKRD13a) acts as a novel component of complex-II to set a higher signal threshold for the cytotoxic potential of TNF. ANKRD13a deficiency is sufficient to turn the response to TNF from survival to death by promoting the formation of complex-II without affecting NF-κB activation. ANKRD13a binds to ubiquitinated-RIP1 via its UIM, and subsequently limits the association of FADD and caspase-8 with RIP1. Moreover, high ANKRD13a expression is inversely correlated with apoptotic phenotypes in ovarian cancer tissues and is associated with poor prognosis. Our work identifies ANKRD13a as a novel gatekeeper of the early cell-death checkpoint, which may function as part of an escape mechanism from cell death in some cancers.

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