• Media type: E-Article
  • Title: Collaboration of Brca1 and Chk2 in tumorigenesis
  • Contributor: McPherson, John Peter; Lemmers, Bénédicte; Hirao, Atsushi; Hakem, Anne; Abraham, Jacinth; Migon, Eva; Matysiak-Zablocki, Elzbieta; Tamblyn, Laura; Sanchez-Sweatman, Otto; Khokha, Rama; Squire, Jeremy; Hande, M. Prakash; Mak, Tak W.; Hakem, Razqallah
  • imprint: Cold Spring Harbor Laboratory, 2004
  • Published in: Genes & Development
  • Language: English
  • DOI: 10.1101/gad.1192704
  • ISSN: 0890-9369; 1549-5477
  • Keywords: Developmental Biology ; Genetics
  • Origination:
  • Footnote:
  • Description: <jats:p>Disruption of <jats:italic>Brca1</jats:italic> results in cellular demise or tumorigenesis depending on cellular context. Inactivation of p53 contributes to <jats:italic>Brca1</jats:italic>-associated tumor susceptibility. However the activation of p53-dependent checkpoint/apoptotic signaling in the absence of <jats:italic>Brca1</jats:italic> is poorly understood. Here, we show that <jats:italic>Chk2</jats:italic> inactivation is partially equivalent to p53 inactivation, in that Chk2 deficiency facilitates the development, survival, and proliferation of Brca1-deficient T cells at the expense of genomic integrity. Brca1 deficiency was found to result in Chk2 phosphorylation and the Chk2-dependent accumulation and activation of p53. Furthermore, inactivation of <jats:italic>Chk2</jats:italic> and <jats:italic>Brca1</jats:italic> was cooperative in breast cancer. Our findings identify a critical role for Chk2 as a component of the DNA damage-signaling pathway activated in response to Brca1 deficiency.</jats:p>
  • Access State: Open Access