title: Cell cycle-dependent conjugation of endogenous BRCA1 protein with SUMO-2/3.
abstract: BACKGROUND
  BRCA1, the main breast and ovarian cancer susceptibility gene, has a key role in maintenance of genome stability, cell cycle and transcription regulation. Interestingly, some of the numerous proteins which interact with BRCA1 protein undergo conjugation with small ubiquitin-like modifiers (SUMO). This post-translational modification is related to transcription, DNA repair, nuclear transport, signal transduction, and to cell cycle stress response.
  
  
  RESULTS
  Protein sequence analysis suggests that sumoylation target sites belong to the RING finger and BRCT domains (BRCA1 C-terminus), two crucial regions for BRCA1 function. Moreover putative SUMO interacting motifs are present in the sequence of many proteins of BRCA1 network. Using immunoprecipitations and western blotting, we show the conjugation of endogenous nuclear BRCA1 protein with SUMO-2/3. BRCA1 conjugation with SUMO-2/3 is linked to the cell cycle in a cell line dependent manner since no cell cycle dependence of sumoylation is observed in MCF7 breast cancer cells. In contrast, BRCA1 conjugation with SUMO-2/3 is linked to the oxidative stress independently to the cell line, in DU145, MCF7 and 293 T cells.
  
  
  CONCLUSIONS
  Our data reveal a new BRCA1 regulation pathway implying sumoylation in response to cell cycle progression and oxidative stress, providing a possible mechanism for the involvement of BRCA1 gene in tumorigenesis.
authors.affiliation: INSERM, U484, Clermont-Ferrand F-63000, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Vialter
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent
authors.forename: Aïcha
authors.initials: A
authors.lastname: Demidem
authors.forename: Daniel
authors.initials: D
authors.lastname: Morvan
authors.forename: Georges
authors.initials: G
authors.lastname: Stepien
authors.forename: Nicole Dalla
authors.initials: ND
authors.lastname: Venezia
authors.forename: Pascale G
authors.initials: PG
authors.lastname: Rio
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019313:BRCA1 Protein / Q000032:analysis / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D025841:Small Ubiquitin-Related Modifier Proteins / Q000032:analysis / Q000378:metabolism*; D058207:Sumoylation
chemical_list: D019313:BRCA1 Protein; D025841:Small Ubiquitin-Related Modifier Proteins