Biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylation
Genetic mutations in HSF4 cause congenital cataracts. HSF4 exhibits both positive and negative regulation on the transcription of heat shock and non-heat shock proteins during lens development, and its activity is regulated by posttranslational modifications. Biotin is an essential vitamin that regu...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580822000280 |
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| author | Longjun Yan Jing Li Jialin Hu Junwei Qu Kejia Li Mingli Wang Shuang-Shuang An Cun-cun Ke Hui Li Fengling Yuan Weikai Guo Mengyue Hu Jing Zhang Zhengyan Yang Hongmei Mu Fengyan zhang Jun Zhang Xiukun Cui Yanzhong Hu |
| author_facet | Longjun Yan Jing Li Jialin Hu Junwei Qu Kejia Li Mingli Wang Shuang-Shuang An Cun-cun Ke Hui Li Fengling Yuan Weikai Guo Mengyue Hu Jing Zhang Zhengyan Yang Hongmei Mu Fengyan zhang Jun Zhang Xiukun Cui Yanzhong Hu |
| author_sort | Longjun Yan |
| collection | DOAJ |
| description | Genetic mutations in HSF4 cause congenital cataracts. HSF4 exhibits both positive and negative regulation on the transcription of heat shock and non-heat shock proteins during lens development, and its activity is regulated by posttranslational modifications. Biotin is an essential vitamin that regulates gene expression through protein biotinylation. In this paper, we report that HSF4b is negatively regulated by biotinylation. Administration of biotin or ectopic bacterial biotin ligase BirA increases HSF4b biotinylation at its C-terminal amino acids from 196 to 493. This attenuates the HSF4b-controlled expression of αB-crystallin in both lens epithelial cells and tested HEK293T cells. HSF4b interacts with holocarboxylase synthetase (HCS), a ubiquitous enzyme for catalyzing protein biotinylation in mammal. Ectopic HA-HCS expression downregulates HSF4b-controlled αB-crystallin expression. Lysine-mutation analyses indicate that HSF4b/K444 is a potential biotinylation site. Mutation K444R reduces the co-precipitation of HSF4b by streptavidin beads and biotin-induced reduction of αB-crystallin expression. Mutations of other lysine residues such as K207R/K209R, K225R, K288R, K294R and K355R in HSF4's C-terminal region do not affect HSF4's expression level and the interaction with streptavidin, but they exhibit distinct regulation on αB-crystallin expression through different mechanisms. HSF4/K294R leads to upregulation of αB-crystallin expression, while mutations K207R/K209R, K225R, K288R, K255R and K435R attenuate HSF4's regulation on αB-crystallin expression. K207R/K209R blocks HSF4 nuclear translocation, and K345R causes HSF4 destabilization. Taken together, the data reveal that biotin maybe a novel factor in modulating HSF4 activity through biotinylation. |
| first_indexed | 2024-12-12T09:39:21Z |
| format | Article |
| id | doaj.art-30f4559da22a4c14a3f989b27b77cf43 |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-12-12T09:39:21Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-30f4559da22a4c14a3f989b27b77cf432022-12-22T00:28:37ZengElsevierBiochemistry and Biophysics Reports2405-58082022-07-0130101227Biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylationLongjun Yan0Jing Li1Jialin Hu2Junwei Qu3Kejia Li4Mingli Wang5Shuang-Shuang An6Cun-cun Ke7Hui Li8Fengling Yuan9Weikai Guo10Mengyue Hu11Jing Zhang12Zhengyan Yang13Hongmei Mu14Fengyan zhang15Jun Zhang16Xiukun Cui17Yanzhong Hu18National-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, ChinaNational-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, ChinaNational-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, ChinaNational-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, ChinaNational-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, ChinaNational-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, ChinaNational-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, ChinaNational-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, ChinaNational-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, ChinaNational-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, ChinaNational-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, ChinaNational-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, ChinaNational-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, ChinaNational-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, ChinaKaifeng Key Lab for Cataract and Myopia, Institute of Eye Disease, Kaifeng Central Hospital, Kaifeng, ChinaDepartment of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaNational-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, ChinaNational-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, China; Corresponding author.National-Joint Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Henan International Union Lab of Antibody Medicine, Department of Cell Biology and Genetics, Henan University School of Basic Medical Sciences, Kaifeng, China; Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Kaifeng Key Lab for Cataract and Myopia, Institute of Eye Disease, Kaifeng Central Hospital, Kaifeng, China; Corresponding author. Department of Cell Biology, Henan University School of Medicine, Zhengzhou, China.Genetic mutations in HSF4 cause congenital cataracts. HSF4 exhibits both positive and negative regulation on the transcription of heat shock and non-heat shock proteins during lens development, and its activity is regulated by posttranslational modifications. Biotin is an essential vitamin that regulates gene expression through protein biotinylation. In this paper, we report that HSF4b is negatively regulated by biotinylation. Administration of biotin or ectopic bacterial biotin ligase BirA increases HSF4b biotinylation at its C-terminal amino acids from 196 to 493. This attenuates the HSF4b-controlled expression of αB-crystallin in both lens epithelial cells and tested HEK293T cells. HSF4b interacts with holocarboxylase synthetase (HCS), a ubiquitous enzyme for catalyzing protein biotinylation in mammal. Ectopic HA-HCS expression downregulates HSF4b-controlled αB-crystallin expression. Lysine-mutation analyses indicate that HSF4b/K444 is a potential biotinylation site. Mutation K444R reduces the co-precipitation of HSF4b by streptavidin beads and biotin-induced reduction of αB-crystallin expression. Mutations of other lysine residues such as K207R/K209R, K225R, K288R, K294R and K355R in HSF4's C-terminal region do not affect HSF4's expression level and the interaction with streptavidin, but they exhibit distinct regulation on αB-crystallin expression through different mechanisms. HSF4/K294R leads to upregulation of αB-crystallin expression, while mutations K207R/K209R, K225R, K288R, K255R and K435R attenuate HSF4's regulation on αB-crystallin expression. K207R/K209R blocks HSF4 nuclear translocation, and K345R causes HSF4 destabilization. Taken together, the data reveal that biotin maybe a novel factor in modulating HSF4 activity through biotinylation.http://www.sciencedirect.com/science/article/pii/S2405580822000280Hsf4BiotinGene mutationαB-crystallinGene transcription |
| spellingShingle | Longjun Yan Jing Li Jialin Hu Junwei Qu Kejia Li Mingli Wang Shuang-Shuang An Cun-cun Ke Hui Li Fengling Yuan Weikai Guo Mengyue Hu Jing Zhang Zhengyan Yang Hongmei Mu Fengyan zhang Jun Zhang Xiukun Cui Yanzhong Hu Biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylation Biochemistry and Biophysics Reports Hsf4 Biotin Gene mutation αB-crystallin Gene transcription |
| title | Biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylation |
| title_full | Biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylation |
| title_fullStr | Biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylation |
| title_full_unstemmed | Biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylation |
| title_short | Biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylation |
| title_sort | biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylation |
| topic | Hsf4 Biotin Gene mutation αB-crystallin Gene transcription |
| url | http://www.sciencedirect.com/science/article/pii/S2405580822000280 |
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