title: Protective effects of thioredoxin-mediated p53 activation in response             to mild hyperthermia.
abstract: Recently, mild hyperthermia was shown to induce cell cycle arrest at the G2/M phase transition without leading to DNA damage. The mechanism of this regulation has not yet been elucidated, although p53 has been shown to be activated in response to mild hyperthermia. Here, we report the role of thioredoxin (TXN) in mild hyperthermia-induced cellular responses. Our data showed that the protein levels of p53 and its downstream gene, Gadd45a, which is an indicator of G2/M arrest, were significantly decreased in TXN siRNA-treated cells under conditions of mild hyperthermia (41˚C, 60 min) as compared to TXN wild-type cells, implying that TXN might play an important role in mild hyperthermia-induced G2/M arrest via p53 and Gadd45a activation. Furthermore, the release of cyclin-dependent kinase Cdc2, known to be regulated by Gadd45a under G2/M arrest, was inhibited from the nucleus for arrest in the G2/M phase in TXN downregulated cells under mild hyperthermia. We suggest that G2/M arrest mediated via the TXN-modulated p53 in response to mild hyperthermia may provide critical insight into the clinical use of mild hyperthermia to induce an adaptive response against genotoxic stresses.
authors: Department of Pharmacology, School of Medicine, Kyung Hee University,                     Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors: Hwa Jin
authors: HJ
authors: Jung
authors: Young Rok
authors: YR
authors: Seo
mesh_terms: D016203:CDC2 Protein Kinase; D059447:Cell Cycle Checkpoints / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases; D004249:DNA Damage / Q000235:genetics; D015536:Down-Regulation; D016195:G2 Phase / Q000235:genetics; D006801:Humans; D006979:Hyperthermia, Induced; D008938:Mitosis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D000097642:GADD45 Proteins
chemical_list: D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins; D019926:Cyclin B; D018844:Cyclin-Dependent Kinases; D009687:Nuclear Proteins; D013879:Thioredoxins; D016159:Tumor Suppressor Protein p53; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C495901:TP53 protein, human; C528899:CDK1 protein, human