The E3 Ubiquitin Ligase Cul4b Promotes CD4+ T Cell Expansion by Aiding the Repair of Damaged DNA

Overview

Journal PLoS Biol

Specialty Biology

Date 2021 Feb 1

PMID 33524014

Citations 14

Authors

Asif A Dar

Keisuke Sawada

Joseph M Dybas

Emily K Moser

Emma L Lewis

Eddie Park

Hossein Fazelinia

Lynn A Spruce

Hua Ding

Steven H Seeholzer

Paula M Oliver

Affiliations

Soon will be listed here.

Abstract

The capacity for T cells to become activated and clonally expand during pathogen invasion is pivotal for protective immunity. Our understanding of how T cell receptor (TCR) signaling prepares cells for this rapid expansion remains limited. Here we provide evidence that the E3 ubiquitin ligase Cullin-4b (Cul4b) regulates this process. The abundance of total and neddylated Cul4b increased following TCR stimulation. Disruption of Cul4b resulted in impaired proliferation and survival of activated T cells. Additionally, Cul4b-deficient CD4+ T cells accumulated DNA damage. In T cells, Cul4b preferentially associated with the substrate receptor DCAF1, and Cul4b and DCAF1 were found to interact with proteins that promote the sensing or repair of damaged DNA. While Cul4b-deficient CD4+ T cells showed evidence of DNA damage sensing, downstream phosphorylation of SMC1A did not occur. These findings reveal an essential role for Cul4b in promoting the repair of damaged DNA to allow survival and expansion of activated T cells.

Citing Articles

The Cullin-RING Ligase Family in Immune Regulation.

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