ATF4 interacts with Abro1/KIAA0157 scaffold protein and participates in a cytoprotective pathway

    Authors

    C. T. Ambivero; L. Cilenti;A. S. Zervos

    Comments

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    Abbreviated Journal Title

    Biochim. Biophys. Acta-Mol. Cell Res.

    Keywords

    Activator protein-1 (AP-1) transcription factor; Activating; transcription factor 4 (ATF4); Abraxas brother 1 (Abro1/KIAA0157); BRCC36 isopeptidase (BRISC) complex; Protein-protein interaction; ENDOPLASMIC-RETICULUM STRESS; DEUBIQUITINATING ENZYMES; OMI/HTRA2; PROTEASE; TUMOR-SUPPRESSOR; CELL-DEATH; UBIQUITIN; COMPLEX; POLYUBIQUITIN; DEGRADATION; ISCHEMIA; Biochemistry & Molecular Biology; Cell Biology

    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. (C) 2012 Elsevier B.V. All rights reserved.

    Journal Title

    Biochimica Et Biophysica Acta-Molecular Cell Research

    Volume

    1823

    Issue/Number

    12

    Publication Date

    1-1-2012

    Document Type

    Article

    Language

    English

    First Page

    2149

    Last Page

    2156

    WOS Identifier

    WOS:000312629200006

    ISSN

    0167-4889

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