title: BCAS2 interacts with HSF4 and negatively regulates its protein stability via ubiquitination.
abstract: Heat shock factor 4 (HSF4) is an important transcriptional factor that plays a vital role in lens development and differentiation, but the mechanism underlying the regulation of HSF4 is ambiguous. BCAS2 was reported to be an essential subunit of pre-mRNA splicing complex. Here, we identified BCAS2 as a novel HSF4 interacting partner. High expression of BCAS2 in the lens epithelium cells and the bow region of mouse lens was detected by immunohistochemistry. In human lens epithelial cells, BCAS2 negatively regulates HSF4 protein level and transcriptional activity, whereas in BCAS2 knockdown cells, HSF4 protein stability was increased significantly. We further demonstrated that the prolonged protein half-time of HSF4 in BCAS2 knockdown cells was due to reduced ubiquitination. Moreover, we have identified the lysine 206 of HSF4 as the key residue for ubiquitination. The HSF4-K206R mutant blocked the impact of BCAS2 on HSF4 protein stability. Taken together, we identified a pathway for HSF4 degradation through the ubiquitin-proteasome system, and a novel function for BCAS2 that may act as a negative regulatory factor for modulating HSF4 protein homeostasis.
authors: Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors: Shengjie
authors: S
authors: Liao
authors: Union Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China.
authors: Rong
authors: R
authors: Du
authors: Department of Pathology & Lab Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA.
authors: Lei
authors: L
authors: Wang
authors: Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors: Zhen
authors: Z
authors: Qu
authors: Key Laboratory of Cellular and Molecular Immunology, Institute of Immunology, Medical College of Henan University, Kaifeng, Henan 475004, PR China.
authors: Xiukun
authors: X
authors: Cui
authors: Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors: Chang
authors: C
authors: Li
authors: Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors: Fei
authors: F
authors: Liu
authors: Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors: Mi
authors: M
authors: Huang
authors: Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors: Jiuxiang
authors: J
authors: Wang
authors: Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors: Jiaxiang
authors: J
authors: Chen
authors: Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors: Meng
authors: M
authors: Gao
authors: Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors: Shanshan
authors: S
authors: Yu
authors: Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors: Zhaohui
authors: Z
authors: Tang
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China; Truhlsen Eye Institute, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors: David Wan-Cheng
authors: DW
authors: Li
authors: Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. Electronic address: tjiang20100@hust.edu.cn.
authors: Tao
authors: T
authors: Jiang
authors: Key Laboratory of Molecular Biophysics of the Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, PR China. Electronic address: lium@mail.hust.edu.cn.
authors: Mugen
authors: M
authors: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D045424:Complex Mixtures / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006801:Humans; D007908:Lens, Crystalline / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D055550:Protein Stability; D059748:Proteolysis; D012326:RNA Splicing; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D054875:Ubiquitination
chemical_list: C120624:BCAS2 protein, human; D045424:Complex Mixtures; D004268:DNA-Binding Proteins; C102948:HSF4 protein, human; D000076249:Heat Shock Transcription Factors; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex
keywords: BCAS2; HSF4; Lens; Ubiquitination; αB-crystallin