title: Heat shock transcription factor 1 down-regulates spermatocyte-specific 70 kDa heat shock protein expression prior to the induction of apoptosis in mouse testes.
abstract: Expression of constitutively active heat shock transcription factor 1 (HSF1) in mouse spermatocytes induces apoptosis and leads to male infertility. We report here that prior to the onset of massive apoptosis caused by expression of active HSF1 in spermatocytes a marked reduction in spermatocyte-specific Hsp70.2 mRNA and protein levels occurs. In addition, HSP70.2 protein relocalizes from a predominant cytoplasmic to a nuclear position in developing spermatocytes that express active HSF1. Later in the developmental stages, cells undergoing HSF1-induced apoptosis essentially lack the HSP70.2 protein. The down-regulation of Hsp70.2 gene expression by HSF1 is paradoxical because HSF1 is the prototypical activator of HSP genes. Furthermore, HSF1-mediated repression neither involved a heat shock element (HSE)-like sequence adjacent to the Hsp70.2 gene nor were Hsp70.2 promoter sequences associated directly with HSF1. Interestingly, other spermatocyte- and spermatid-specific transcripts are also down-regulated in testes of transgenic mice expressing active HSF1, suggesting involvement of a putative HSF1-dependent block of development of spermatogenic cells. Importantly however, transcription of the Hsp70.2 gene is down-regulated in testes of wild-type mice subjected to a hyperthermia that induces transient activation of HSF1, indicating that the spermatocyte-specific activity of HSF1 might misdirect a network of transcription factors required for proper regulation of Hsp70.2.
authors.affiliation: Department of Tumor Biology, Maria Sklodowksa-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, 44-101 Gliwice, Poland. wwidlak@io.gliwice.pl
authors.forename: Wieslawa
authors.initials: W
authors.lastname: Widlak
authors.forename: Natalia
authors.initials: N
authors.lastname: Vydra
authors.forename: Ewa
authors.initials: E
authors.lastname: Malusecka
authors.forename: Volha
authors.initials: V
authors.lastname: Dudaladava
authors.forename: Boleslaw
authors.initials: B
authors.lastname: Winiarski
authors.forename: Dorota
authors.initials: D
authors.lastname: Scieglińska
authors.forename: Piotr
authors.initials: P
authors.lastname: Widlak
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005334:Fever; D018507:Gene Expression Regulation, Developmental; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D020218:Response Elements; D013090:Spermatocytes / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; C490434:Hspa2 protein, mouse; D014157:Transcription Factors