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| Subject Categories: Proteins | Development |
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| The EMBO Journal
(2004) 23, 4297–4306, doi:10.1038/sj.emboj.7600435 Published online 14 October 2004 |
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| HSF4 is required for normal cell growth and differentiation during mouse lens development |
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| Mitsuaki Fujimoto1, Hanae Izu1, Keisuke Seki2, Ken Fukuda2, Teruo Nishida2, Shu-ichi Yamada3, Kanefusa Kato4, Shigenobu Yonemura5, Sachiye Inouye1 and Akira Nakai1 |
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1 Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Ube, Japan 2 Department of Biomolecular Recognition and Ophthalmology, Yamaguchi University School of Medicine, Ube, Japan 3 Department of Cell Biology, Institute for Virus Research, Kyoto University, Kyoto, Japan 4 Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan 5 Laboratory for Cellular Morphogenesis, RIKEN Center for Developmental Biology, Kobe, Japan To whom correspondence should be addressed Akira Nakai, Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Minami-Kogushi 1-1-1, Ube 755-8505, Japan. Tel.: +81 836 22 2214; Fax: +81 836 22 2315; E-mail: anakai@yamaguchi-u.ac.jp Received 22 April 2004; Accepted 13 September 2004; Published online 14 October 2004. |
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| Abstract |
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The heat shock transcription factor (HSF) family consists of three members in mammals and regulates expression of heat shock genes via a heat shock element. HSF1 and HSF2 are required for some developmental processes, but it is unclear how they regulate these processes. To elucidate the mechanisms of developmental regulation by HSFs, we generated mice in which the HSF4 gene is mutated. HSF4-null mice had cataract with abnormal lens fiber cells containing inclusion-like structures, probably due to decreased expression of  -crystallin, which maintains protein stability. Furthermore, we found increased proliferation and premature differentiation of the mutant lens epithelial cells, which is associated with increased expression of growth factors, FGF-1, FGF-4, and FGF-7. Unexpectedly, HSF1 competed with HSF4 for the expression of FGFs not only in the lens but also in other tissues. These findings reveal the lens-specific role of HSF4, which activates -crystallin genes, and also indicate that HSF1 and HSF4 are involved in regulating expression of growth factor genes, which are essential for cell growth and differentiation. |
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| Keywords: crystallin, FGF, heat shock, lens, transcription |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHMolecular Therapy Original Article Rho GTPase Inactivation Impairs Lens Growth and Integrity Laboratory Investigation Article Response Regulation of αA-crystallin via Pax6, c-Maf, CREB and a broad domain of lens-specific chromatin The EMBO Journal Article (17 May 2006) A novel HSF1-mediated death pathway that is suppressed by heat shock proteins The EMBO Journal Article (18 Oct 2006) |
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