Title

Atf4 Interacts With Abro1/Kiaa0157 Scaffold Protein And Participates In A Cytoprotective Pathway

Keywords

Abraxas brother 1 (Abro1/KIAA0157); Activating transcription factor 4 (ATF4); Activator protein-1 (AP-1) transcription factor; BRCC36 isopeptidase (BRISC) complex; Protein-protein interaction

Abstract

Abro1 (Abraxas brother 1), also known as KIAA0157, is a scaffold protein that recruits various polypeptides to assemble the BRISC (BRCC36 isopeptide) deubiquitinating enzyme (DUB) complex. The BRISC enzyme has a Lys63-linked deubiquitinating activity and is comprised of four known subunits: MERIT40 (mediator of Rap80 interactions and targeting 40. kDa), BRE (brain and reproductive organ-expressed), BRCC36 (BRCA1/BRCA2-containing complex, subunit 3) and Abro1. We have previously shown that Abro1 has a cytoprotective role that involves the BRISC DUB complex acting on specific Lys63-linked polyubiquitinated substrates. In this report we identify three members of the AP-1 (activating protein-1) family, the ATF4, ATF5 (activating transcription factor) and JunD proteins, as specific interactors of Abro1. The function of ATF4-Abro1 interaction was investigated under normal conditions as well as under cellular stress. Abro1 is predominantly cytoplasmic, but during cellular stress it enters the nucleus and co-localizes with ATF4. Furthermore, this interaction with ATF4 is necessary and essential for the cytoprotective function of Abro1 following oxidative stress. The ability of Abro1 to specifically interact with a number of transcription factors suggests a new mechanism of regulation of the BRISC DUB complex. This regulation involves the participation of at least three known members of the AP-1 family of transcription factors. © 2012 Elsevier B.V.

Publication Date

12-1-2012

Publication Title

Biochimica et Biophysica Acta - Molecular Cell Research

Volume

1823

Issue

12

Number of Pages

2149-2156

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1016/j.bbamcr.2012.08.020

Socpus ID

84867301032 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84867301032

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