ANKRD13a controls early cell-death checkpoint by interacting with RIP1 independent of NF-κB

Autor: Won, Minho, Park, Kyeong Ah, Kim, Sup, Ju, Eunjin, Ko, Youngbok, Yoo, Heonjong, Ro, Hyunju, Lee, Jaeseob, Oh, Junseo, Lee, Eun Gyo, Kim, Sang Yean, Nam, Suk Woo, Shen, Han-Ming, Yeo, Min-Kyung, Kim, Jin Man, Hur, Gang Min
Zdroj: Cell Death and Differentiation; June 2022, Vol. 29 Issue: 6 p1152-1163, 12p
Abstrakt: 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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