title: Functional HSF1 requires aromatic-participant interactions in protecting mouse embryonic fibroblasts against apoptosis via G2 cell cycle arrest.
abstract: The present study highlighted the aromatic-participant interactions in in vivo trimerization of HSF1 and got an insight into the process of HSF1 protecting against apoptosis. In mouse embryonic fibroblasts (MEFs), mutations of mouse HSF1 (W37A, Y60A and F104A) resulted in a loss of trimerization activity, impaired binding of the heat shock element (HSE) and lack of heat shock protein 70 (HSP70) expression after a heat shock. Under UV irradiation, wild-type mouse HSF1 protected the MEFs from UV-induced apoptosis, but none of the mutants offered protection. We found that normal expression of HSF1 was essential to the cell arrest in G2 phase, assisting with the cell cycle checkpoint. The cells that lack normal HSF1 failed to arrest in the G2 phase, resulting in the process of cell apoptosis. We conclude that the treatment with UV or heat shock stresses appears to induce the approach of HSF1 monomers directly via aromatic-participant interactions, followed by the formation of a HSF1 trimer. HSF1 protects the MEFs from the stresses through the expression of HSPs and a G2 cell cycle arrest.
authors.affiliation: Department of Chemistry and Chemistry Institute of Functional Materials, Pusan National University, Busan 609-735, Korea.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Chang
authors.forename: Ming
authors.initials: M
authors.lastname: Lu
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Park
authors.forename: Hyun-Kyung
authors.initials: HK
authors.lastname: Park
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Kang
authors.forename: Youngshang
authors.initials: Y
authors.lastname: Pak
authors.forename: Jang-Su
authors.initials: JS
authors.lastname: Park
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000235:genetics; D051379:Mice; D009154:Mutation; D011485:Protein Binding; D055503:Protein Multimerization; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; D014157:Transcription Factors