title: Cdc25A promotes cell survival by stimulating NF-κB activity through IκB-α phosphorylation and destabilization.
abstract: Cell division cycle 25A (Cdc25A), a dual specificity protein phosphatase, exhibits anti-apoptotic activity, but the underlying molecular mechanisms are poorly characterized. Here we report that Cdc25A inhibits cisplatin-induced apoptotic cell death by stimulating nuclear factor-kappa B (NF-κB) activity. In HEK-293 cells, Cdc25A decreased protein level of inhibitor subunit kappa B alpha (Iκ-Bα) in association with increased serine 32-phosphorylation, followed by stimulation of transcriptional activity of NF-κB. Inhibition of NF-κB activity by chemical inhibitor or overexpression of Iκ-Bα in Cdc25A-elevated cancer cells resistant to cisplatin improved their sensitivity to cisplatin-induced apoptosis. Our data show for the first time that Cdc25A has an important physiological role in NF-κB activity regulation and it may be an important survival mechanism of cancer cells.
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, 192-1 Hyoja-2-dong, Chuncheon 200-701, Republic of Korea.
authors.forename: Hey-Young
authors.initials: HY
authors.lastname: Hong
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Choi
authors.forename: Young-Wook
authors.initials: YW
authors.lastname: Cho
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D051996:Transcription Factor RelA / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D051996:Transcription Factor RelA; D051550:I-kappa B Kinase; C517004:CDC25A protein, human; D020687:cdc25 Phosphatases; D002945:Cisplatin