title: Heat shock factor 1-mediated aneuploidy requires a defective function of p53.
abstract: Because heat shock factor 1 (HSF1) phosphorylation by Plk1 has been previously reported to be involved in mitotic regulation and p53 function may be involved in this mitotic regulation, we have further examined HSF1 functions in mitotic regulation according to p53 status. Nocodazole-mediated aneuploidy was increased in p53-defective (p53Mut) cells; however, it was not increased in p53 wild-type (p53WT) cells. Phosphorylation of HSF1 at Ser216 was increased in p53Mut cells with increased stability of securin and cyclin B1 in mitosis compared with p53WT cells. The interaction of p53 with Plk1 that was shown in p53WT cells and that induced normal mitotic checkpoint function was not observed in p53Mut cells; instead, the binding of HSF1 with Plk1 and HSF1 phosphorylation at Ser216 were seen in p53Mut cells, which resulted in increased aneuploidy production. Moreover, the interaction affinity of Cdc20 with Mad2 was inhibited in p53Mut cells, whereas the interaction between Cdc20 and HSF1 was increased. From the data, it was suggested that HSF1-mediated aneuploidy was more facilitated in p53-defective cells, indicating the importance of novel mechanisms for p53 function in HSF1-mediated mitotic regulation and genomic instability.
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
authors.forename: Eun-Ho
authors.initials: EH
authors.lastname: Kim
authors.forename: Yoon-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Sangwoo
authors.initials: S
authors.lastname: Bae
authors.forename: Jae Seon
authors.initials: JS
authors.lastname: Lee
authors.forename: Joon
authors.initials: J
authors.lastname: Kim
authors.forename: Yun-Sil
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000782:Aneuploidy; D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D045325:HCT116 Cells; D000076249:Heat Shock Transcription Factors; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D064246:Mad2 Proteins; D051379:Mice; D018345:Mice, Knockout; D015739:Nocodazole / Q000494:pharmacology; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D002135:Calcium-Binding Proteins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D064246:Mad2 Proteins; D015739:Nocodazole; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000097869:Polo-Like Kinase 1; C000619706:HSF1 protein, human; C577697:MAD2L1 protein, human; C495901:TP53 protein, human; C577488:CDC20 protein, human