title: The transcription activity of heat shock factor 4b is regulated by FGF2.
abstract: Heat shock factor 4b has been found to be closely associated with postnatal lens development. It expresses in postnatal lens epithelial and secondary fiber cells and controls the expression of small heat shock proteins which are important for lens homeostasis. However, the signal pathways underlying Hsf4b are still not completely understood. Here we present that Hsf4b transcription activity is regulated by FGF2 a key growth factor that is involved in regulating lens development at multiple stages. FGF2 can promote Hsf4b nuclear-translocation and the expression of Hsp25 and αB-crystallin, the key downstream targets of Hsf4b in the Hsf4b-reconstituted mouse hsf4-/- lens epithelial cells. Further study indicates that FGF2 can induce Hsf4b protein stabilization through ERK1/2-mediated posttranslational phosphorylation or sumoylation. Hsf4b can promote FGF2-induced morphology transition from lens epithelial cell to the fiber cell, and this morphology transition can be inhibited by ERK1/2 inhibitor U0126. Taken together, our data demonstrate that Hsf4b is a novel downstream transcription factor of FGF2, and its transcription activity is associated with FGF2-modulated lens epithelial cell-fiber cell transition.
authors.affiliation: Key Laboratory of Molecular and Cellular Immunology, Hunan University School of Medicine, Jin-Ming Road, Kaifeng, Henan, China. hyz@henu.edu.cn
authors.forename: Yan-Zhong
authors.initials: YZ
authors.lastname: Hu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Shulian
authors.initials: S
authors.lastname: Li
authors.forename: Chuan
authors.initials: C
authors.lastname: Wang
authors.forename: Liujie
authors.initials: L
authors.lastname: Chu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zengyi
authors.initials: Z
authors.lastname: Ma
authors.forename: Mingli
authors.initials: M
authors.lastname: Wang
authors.forename: Qiying
authors.initials: Q
authors.lastname: Jiang
authors.forename: Guangchao
authors.initials: G
authors.lastname: Liu
authors.forename: Yijun
authors.initials: Y
authors.lastname: Qi
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D048430:Cell Shape; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D057809:HEK293 Cells; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D059748:Proteolysis; D058207:Sumoylation; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D015854:Up-Regulation; D038203:alpha-Crystallin B Chain / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; C484462:Hsf4 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D014157:Transcription Factors; D038203:alpha-Crystallin B Chain; D016222:Fibroblast Growth Factor 2; D048049:Extracellular Signal-Regulated MAP Kinases