2013
DOI: 10.1074/jbc.m113.467662
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4-Hydroxynonenal Induces G2/M Phase Cell Cycle Arrest by Activation of the Ataxia Telangiectasia Mutated and Rad3-related Protein (ATR)/Checkpoint Kinase 1 (Chk1) Signaling Pathway

Abstract: Background: HNE is an important signaling molecule. Results: HNE induces G 2 /M cell cycle arrest and phosphorylation of H2A.X. ATR/Chk1-mediated regulation of Cdc25C and activation of p21 is the predominant mechanism of HNE-induced cell cycle arrest. GSTA4-4 overexpression inhibits HNEinduced cell arrest. Conclusion: HNE causes DNA damage and G 2 /M arrest. Significance: HNE and GSTA4-4 play a role in the maintenance of genomic integrity.

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Cited by 50 publications
(60 citation statements)
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“…Downregulation of cyclin B1‐CDK1 expression was more evident than that of cyclin A‐CDK2 or cyclin A‐CDK1 in MB cells following treatment with IAP antagonist or in combination with vincristine or cisplatin. These data are in accordance with other studies showing that attenuation of the cyclin B1‐CDK1 complex, which is critical for entry into mitotic phase, can be seen in cancer cells arresting in the G2/M transition 30, 31…”
Section: Resultssupporting
confidence: 93%
“…Downregulation of cyclin B1‐CDK1 expression was more evident than that of cyclin A‐CDK2 or cyclin A‐CDK1 in MB cells following treatment with IAP antagonist or in combination with vincristine or cisplatin. These data are in accordance with other studies showing that attenuation of the cyclin B1‐CDK1 complex, which is critical for entry into mitotic phase, can be seen in cancer cells arresting in the G2/M transition 30, 31…”
Section: Resultssupporting
confidence: 93%
“…The DDR preserves genetic stability by detecting DNA lesions, activating cell cycle checkpoints and promoting DNA damage repair [18][19][20][21]. The common denominator integrating these forms of genotoxic stresses and eliciting the signalling cascade is increased production of ROS as harbinger to DNA damage [22][23][24][25][26][27]. Chemical agents such as drugs used in cancer chemotherapy are also able to induce some form of DNA lesions [28].…”
Section: Introductionmentioning
confidence: 99%
“…Since we did not observe the reduction of phospho-ERK in NT2/D1 cells after nanomolar levels of TBT exposure (data not shown), the mechanism of inducing G2 arrest may differ depending on the TBT levels and cell type. Moreover, several chemical stressors have been reported to cause G2/M cell cycle arrest through the protein reduction of cell cycle regulators (Chaudhary et al, 2013;Nam et al, 2010;Ouyang et al, 2009). For instance, 4-Hydroxynonenal, an inducer of oxidative stress, causes DNA damage and induces G2/M cell cycle arrest in hepatocellular carcinoma HepG2 and Hep3B cells, following reduction of cdc25C and thereafter cyclin B1 proteins in a p53-independent manner (Chaudhary et al, 2013).…”
Section: Discussionmentioning
confidence: 99%
“…Protein levels of these cell cycle regulators are strictly regulated during cell cycle progression. Ultraviolet irradiation or toxic drugs are known to cause G2 arrest by the inactivation of cyclin B1/Cdk1 via p53 induction followed by the upregulation of p21, a Cdk inhibitor and/or cdc25C downregulation by degradation (Chaudhary et al, 2013;Kawabe, 2004;Nam et al, 2010;Ouyang et al, 2009).…”
Section: Introductionmentioning
confidence: 99%