title: Tumor suppressor CHK2: regulator of DNA damage response and mediator of chromosomal stability.
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.
authors.affiliation: Department of Molecular Oncology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Ailine
authors.initials: A
authors.lastname: Stolz
authors.forename: Norman
authors.initials: N
authors.lastname: Ertych
authors.forename: Holger
authors.initials: H
authors.lastname: Bastians
mesh_terms: D017209:Apoptosis; D064447:Checkpoint Kinase 2; D043171:Chromosomal Instability; D004249:DNA Damage; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: D025521:Tumor Suppressor Proteins; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases