| Full Name | Checkpoint Kinase 2 |
|---|---|
| Chromosomal Location | 22q12.1 |
| NCBI Gene ID | 1111 |
| OMIM | 604373 |
| Ensembl ID | ENSG00000149554 |
| UniProt ID | O96017 |
| Protein | CHEK2 protein |
| Associated Diseases | Li-Fraumeni syndrome variant, Prostate cancer, Breast cancer, Osteosarcoma, Glioma |
Checkpoint kinase 2 (CHEK2) is a serine/threonine-protein kinase encoded by the CHEK2 gene located on chromosome 22q12.1[1]. CHEK2 plays a critical role in maintaining genomic stability through its involvement in the DNA damage checkpoint pathway. As a key effector of ATM-mediated DNA damage response, CHEK2 helps coordinate cell cycle arrest, DNA repair, and apoptosis in response to genotoxic stress[2].
Mutations in CHEK2 have been associated with increased cancer risk, particularly in the context of Li-Fraumeni-like syndromes. The protein's kinase activity is regulated by phosphorylation in response to DNA double-strand breaks, making it a potential therapeutic target in cancers with defective DNA repair mechanisms.
| Full Name | Checkpoint Kinase 2 |
|---|---|
| Chromosomal Location | 22q12.1 |
| NCBI Gene ID | 1111 |
| OMIM | 604373 |
| Ensembl ID | ENSG00000149554 |
| UniProt ID | O96017 |
| Protein | CHEK2 protein |
| Associated Diseases | Li-Fraumeni syndrome variant, Prostate cancer, Breast cancer, Osteosarcoma, Glioma |
Checkpoint kinase 2 (CHEK2) is a serine/threonine-protein kinase that plays a critical role in the DNA damage checkpoint pathway[1:1]. In response to DNA double-strand breaks (DSBs), ATM kinase phosphorylates CHEK2 at Thr68, activating its kinase activity[2:1]. Activated CHEK2 then phosphorylates multiple downstream targets including:
CHEK2 exists as a dimer that undergoes trans-autophosphorylation upon DNA damage[7]. The protein contains an N-terminal SQ/TQ cluster domain (SCD) with multiple ATM phosphorylation sites, a central forkhead-associated (FHA) domain, and a C-terminal kinase domain[8].
CHEK2 is ubiquitously expressed in human tissues with highest levels in testis, thymus, and prostate[15]. In the brain, CHEK2 is expressed in:
Expression increases in response to DNA damage, oxidative stress, and during aging[17].
Ahn J, et al. Human CHK2 protein kinase. Oncogene. 2000. ↩︎ ↩︎
Matsuoka S, et al. ATM and CHK2 target network. Cell. 2000. ↩︎ ↩︎
Chehab NH, et al. Chk2/hCds1 functions as a DNA damage checkpoint. Genes Dev. 2000. ↩︎
Zhou BB, Bartek J. Targeting the checkpoint kinases. Nat Rev Cancer. 2004. ↩︎
Zhang J, et al. BRCA1 regulates CHK2. Mol Cell. 2003. ↩︎
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Bane AL, et al. CHEK2 I157T and breast cancer. Breast Cancer Res. 2007. ↩︎
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Jhaveri K, et al. CHK2 in Parkinson's disease models. Neurosci Lett. 2013. ↩︎
Sathasivam K, et al. DNA damage in ALS. Brain. 2014. ↩︎
U.S. National Library of Medicine. CHEK2 expression atlas. ↩︎
Inoue M, et al. Neuronal CHK2 expression. Brain Res Mol Brain Res. 2002. ↩︎
Rashi-Elkeles S, et al. DNA damage response and aging. Aging Cell. 2011. ↩︎
Antoni L, et al. CHK2 inhibitors in cancer therapy. Nat Rev Cancer. 2007. ↩︎
Zhou ZR, et al. Targeting DNA damage response in cancer therapy. J Natl Cancer Inst. 2014. ↩︎