title: DNA-binding and transcriptional activities of human HSF4 containing mutations that associate with congenital and age-related cataracts.
abstract: Heat shock transcription factor HSF4 is necessary for ocular lens development and fiber cell differentiation. Mutations of the human HSF4 gene have been implicated in congenital and age-related cataracts. Here, we show that HSF4 activates transcription of genes encoding crystallins and beaded filament structural proteins in lens epithelial cells. Five missense mutations that have been associated with congenital cataract inhibited DNA-binding of HSF4, which demonstrates the relationship between HSF4 mutations, loss of lens protein gene expression, and cataractogenesis. However, two missense mutations that have been associated with age-related cataract did not or only slightly alter HSF4 activity, implying that other genetic and environmental factors affect the functions of these mutant proteins.
authors.affiliation: Division of Health Sciences, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-0942, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Enoki
authors.forename: Yuka
authors.initials: Y
authors.lastname: Mukoda
authors.forename: Chie
authors.initials: C
authors.lastname: Furutani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakurai
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D002386:Cataract / Q000151:congenital / Q000235:genetics*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D017930:Genes, Reporter; D006367:HeLa Cells; D000076249:Heat Shock Transcription Factors; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020125:Mutation, Missense / Q000502:physiology; D011485:Protein Binding; D055503:Protein Multimerization / Q000235:genetics; D020218:Response Elements; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C102948:HSF4 protein, human; D000076249:Heat Shock Transcription Factors; D050505:Mutant Proteins; D014157:Transcription Factors; D004247:DNA