Role of CHK2 in cancer development

Perona, Rosario; Moncho-Amor, Verónica; Machado-Pinilla, Rosario; Belda-Iniesta, Cristóbal; Sanchez-Perez, Isabel

doi:10.1007/s12094-008-0248-5

Cited by 35 publications

(33 citation statements)

References 35 publications

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“…Several studies have identified CHK2 as a multiorgan cancer susceptibility gene that is mutated in both somatic and hereditary human cancers, including breast, colon, prostate, and lung carcinomas, albeit at low frequencies (3,28). In addition, investigators have reported a loss of the CHK2 locus on chromosome 22q13 in breast, colorectal, ovarian, and brain tumors (29)(30)(31), and epigenetic silencing of CHK2 expression in lung cancer (32).…”

Section: Chk2 Alterations In Human Cancermentioning

confidence: 99%

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

Stolz

Ertych

Bastians

2011

Clinical Cancer Research

101

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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.

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Section: Chk2 Alterations In Human Cancermentioning

confidence: 99%

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

Stolz

Ertych

Bastians

2011

Clinical Cancer Research

101

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“…ATM phosphorylates Chk2 leading to activation of cell cycle checkpoints. Chk2 acts as a signal distributor, dispersing checkpoint signal to downstream targets such as p53, Cdc25A, Cdc25C, BRCA1 and E2F1 [17].…”

Section: Introductionmentioning

confidence: 99%

Expression of the Genetic Suppressor Element 24.2 (GSE24.2) Decreases DNA Damage and Oxidative Stress in X-Linked Dyskeratosis Congenita Cells

et al. 2014

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The predominant X-linked form of Dyskeratosis congenita results from mutations in DKC1, which encodes dyskerin, a protein required for ribosomal RNA modification that is also a component of the telomerase complex. We have previously found that expression of an internal fragment of dyskerin (GSE24.2) rescues telomerase activity in X-linked dyskeratosis congenita (X-DC) patient cells. Here we have found that an increased basal and induced DNA damage response occurred in X-DC cells in comparison with normal cells. DNA damage that is also localized in telomeres results in increased heterochromatin formation and senescence. Expression of a cDNA coding for GSE24.2 rescues both global and telomeric DNA damage. Furthermore, transfection of bacterial purified or a chemically synthesized GSE24.2 peptide is able to rescue basal DNA damage in X-DC cells. We have also observed an increase in oxidative stress in X-DC cells and expression of GSE24.2 was able to diminish it. Altogether our data indicated that supplying GSE24.2, either from a cDNA vector or as a peptide reduces the pathogenic effects of Dkc1 mutations and suggests a novel therapeutic approach.

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“…Chk2 phosphorylates other substrates such as p53 leading to DNA repair, apoptosis, or G1 arrest. 14,15 In addition, TRF2 (telomeric repeat factor 2) binds to double-stranded telomeric DNA and is involved in telomere length maintenance and the protection of telomere end capping. TRF2 may act as an early component of the DNA repair system with migration to specific sites of DNA damage in response to DSBs.…”

mentioning

confidence: 99%

DNA Damage Signaling and Apoptosis in Preinvasive Tubal Lesions of Ovarian Carcinoma

Chêne

Ouellet

Rahimi

et al. 2015

International Journal of Gynecological Cancer

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Role of CHK2 in cancer development

Cited by 35 publications

References 35 publications

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

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

Expression of the Genetic Suppressor Element 24.2 (GSE24.2) Decreases DNA Damage and Oxidative Stress in X-Linked Dyskeratosis Congenita Cells

DNA Damage Signaling and Apoptosis in Preinvasive Tubal Lesions of Ovarian Carcinoma

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