Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 17 (3), 401-5

Tumor Suppressor CHK2: Regulator of DNA Damage Response and Mediator of Chromosomal Stability

Affiliations

Tumor Suppressor CHK2: Regulator of DNA Damage Response and Mediator of Chromosomal Stability

Ailine Stolz et al. Clin Cancer Res.

Abstract

CHK2 is a multiorgan tumor susceptibility gene that encodes for a serine/threonine protein kinase involved in the response to cellular DNA damage. After ATM-mediated phosphorylation, the activated Chk2 kinase can act as a signal transducer and phosphorylate a variety of substrates, including the Cdc25 phosphatases, p53, PML, E2F-1, and Brca1, which has been associated with halting the cell cycle, the initiation of DNA repair, and the induction of apoptosis after DNA damage. In addition, recent work has revealed another, DNA-damage-independent function of Chk2 during mitosis that is required for proper mitotic spindle assembly and maintenance of chromosomal stability. This novel role involves a mitotic phosphorylation of the tumor suppressor Brca1 by the Chk2 kinase. On the basis of its role during DNA damage response, Chk2 has been suggested as an anticancer therapy target, but given its recently discovered new function and its role as a tumor suppressor, it is questionable whether inhibition of Chk2 is indeed beneficial for anticancer treatment. However, investigators may be able to exploit the loss of CHK2 in human tumors to develop novel therapies based on synthetic lethal interactions.

Similar articles

See all similar articles

Cited by 31 PubMed Central articles

See all "Cited by" articles

Substances

LinkOut - more resources

Feedback