K33-linked Polyubiquitination of Zap70 by Nrdp1 Controls CD8(+) T Cell Activation

Overview

Journal Nat Immunol

Date 2015 Sep 22

PMID 26390156

Citations 60

Authors

Mingjin Yang

Taoyong Chen

Xuelian Li

Zhou Yu

Songqing Tang

Chen Wang

Yan Gu

Yanfang Liu

Sheng Xu

Weihua Li

Xuemin Zhang

Jianli Wang

Xuetao Cao

Affiliations

Soon will be listed here.

Abstract

The key molecular mechanisms that control signaling via T cell antigen receptors (TCRs) remain to be fully elucidated. Here we found that Nrdp1, a ring finger-type E3 ligase, mediated Lys33 (K33)-linked polyubiquitination of the signaling kinase Zap70 and promoted the dephosphorylation of Zap70 by the acidic phosphatase-like proteins Sts1 and Sts2 and thereby terminated early TCR signaling in CD8(+) T cells. Nrdp1 deficiency significantly promoted the activation of naive CD8(+) T cells but not that of naive CD4(+) T cells after engagement of the TCR. Nrdp1 interacted with Zap70 and with Sts1 and Sts2 and connected K33 linkage of Zap70 to Sts1- and Sts2-mediated dephosphorylation. Our study suggests that Nrdp1 terminates early TCR signaling by inactivating Zap70 and provides new mechanistic insights into the non-proteolytic regulation of TCR signaling by E3 ligases.

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