CtBP/BARS: a dual-function protein involved in transcription co-repression and Golgi membrane fission

Marco Nardini, Stefania Spanò, Claudia Cericola, Alessandra Pesce, Anna Massaro, Enrico Millo, Alberto Luini, Daniela Corda, Martino Bolognesi

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)3122-30
Number of pages9
JournalEMBO Journal
Volume22
Issue number12
DOIs
Publication statusPublished - 16 Jun 2003

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Keywords

  • Acyl Coenzyme A
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Carrier Proteins
  • Cell Membrane
  • Crystallography, X-Ray
  • Golgi Apparatus
  • Models, Molecular
  • Molecular Sequence Data
  • NAD
  • Peptides
  • Protein Binding
  • Protein Folding
  • Protein Structure, Tertiary
  • Rats
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Sequence Alignment
  • Transcription Factors
  • Transcription, Genetic

Cite this

Nardini, M., Spanò, S., Cericola, C., Pesce, A., Massaro, A., Millo, E., ... Bolognesi, M. (2003). CtBP/BARS: a dual-function protein involved in transcription co-repression and Golgi membrane fission. EMBO Journal, 22(12), 3122-30. https://doi.org/10.1093/emboj/cdg283