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CtBP/BARS: a dual‐function protein involved in transcription co‐repression and Golgi membrane fission
Author(s) -
Nardini Marco,
Spanò Stefania,
Cericola Claudia,
Pesce Alessandra,
Massaro Anna,
Millo Enrico,
Luini Alberto,
Corda Daniela,
Bolognesi Martino
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg283
Subject(s) - biology , psychological repression , microbiology and biotechnology , golgi apparatus , fission , transcription (linguistics) , transcription factor , dual role , dual (grammatical number) , genetics , endoplasmic reticulum , gene expression , gene , physics , art , linguistics , philosophy , chemistry , literature , quantum mechanics , neutron , combinatorial chemistry
C‐terminal‐binding protein/brefeldin A‐ADP ribosylated substrate (CtBP/BARS) plays key roles in development and oncogenesis as a transcription co‐repressor, and in intracellular traffic as a promoter of Golgi membrane fission. Co‐repressor activity is regulated by NAD(H) binding to CtBP/BARS, while membrane fission is associated with its acyl‐CoA‐dependent acyltransferase activity. Here, we report the crystal structures of rat CtBP/BARS in a binary complex with NAD(H), and in a ternary complex with a PIDLSKK peptide mimicking the consensus motif (PXDLS) recognized in CtBP/BARS cellular partners. The structural data show CtBP/BARS in a NAD(H)‐bound dimeric form; the peptide binding maps the recognition site for DNA‐binding proteins and histone deacetylases to an N‐terminal region of the protein. The crystal structure together with the site‐directed mutagenesis data and binding experiments suggest a rationale for the molecular mechanisms underlying the two fundamental co‐existing, but diverse, activities supported by CtBP/BARS in the nucleus and in Golgi membranes.