Biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylation.
Biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylation.
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生物素通过赖氨酸 444 生物素化减弱热休克因子 4b 转录活性
DOI：
10.1016/j.bbrep.2022.101227
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发表时间：
2022-07
影响因子：
2.7
通讯作者：
Hu Y
中科院分区：
文献类型：
--
作者：
Yan L;Li J;Hu J;Qu J;Li K;Wang M;An SS;Ke CC;Li H;Yuan F;Guo W;Hu M;Zhang J;Yang Z;Mu H;Zhang F;Zhang J;Cui X;Hu Y
HSF 4基因突变导致先天性白内障。在透镜发育过程中，HSF 4对热休克蛋白和非热休克蛋白的转录具有正调控和负调控作用，其活性受翻译后修饰的调控。生物素是一种必需的维生素，通过蛋白质生物素化调节基因表达。在本文中，我们报告HSF 4 b是负调控的生物素化。施用生物素或异位细菌生物素连接酶BirA使HSF 4 b在其C-末端氨基酸处的生物素化从196增加至493。这减弱了透镜上皮细胞和测试的HEK 293 T细胞中HSF 4 b控制的α B-晶状体蛋白的表达。HSF 4 b与全羧化酶合成酶（HCS）相互作用，全羧化酶合成酶是哺乳动物中普遍存在的催化蛋白质生物素化的酶。异位HA-HCS表达下调HSF 4 b控制的α B-晶状体蛋白表达。赖氨酸突变分析表明，HSF 4 b/K444是一个潜在的生物素化位点。突变K444 R减少了链霉亲和素珠与HSF 4 b的共沉淀以及生物素诱导的α B-晶状体蛋白表达减少。HSF 4 C端其他赖氨酸残基如K207 R/K209 R、K225 R、K288 R、K294 R和K355 R的突变不影响HSF 4的表达水平及其与链霉亲和素的相互作用，但它们通过不同的机制对α B-晶状体蛋白的表达有不同的调节作用。HSF 4/K294 R导致α B-晶状体蛋白表达上调，而突变K207 R/K209 R、K225 R、K288 R、K255 R和K435 R减弱HSF 4对α B-晶状体蛋白表达的调节。K207 R/K209 R阻断HSF 4核转位，K345 R导致HSF 4不稳定。综上所述，数据表明，生物素可能是一种新的因素，在调节HSF 4的活性，通过生物素化。生物素下调HSF 4的转录活性。HSF 4与全羧化酶合成酶（HCS）相关并被其下调。K444是HSF 4 b中潜在的生物素化氨基酸残基。
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. Biotin downregulates HSF4's transcription activity. HSF4 is associated with and down-regulated by holocarboxylase synthetase (HCS). K444 is the potential biotinylated amino acid residue in HSF4b.
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影响因子：
3.8
作者：
Kuroishi, Toshinobu;Rios-Avila, Luisa;Pestinger, Valerie;Wijeratne, Subhashinee S. K.;Zempleni, Janos
通讯作者：
Zempleni, Janos
DOI：
10.1073/pnas.1332608100
发表时间：
2003-06-24
影响因子：
11.1
作者：
de Boer, E;Rodriguez, P;Strouboulis, J
通讯作者：
Strouboulis, J
影响因子：
5.6
作者：
Rios-Avila, Luisa;Pestinger, Valerie;Zempleni, Janos
通讯作者：
Zempleni, Janos
DOI：
10.1196/annals.1391.005
发表时间：
2007-01-01
期刊：
STRESS RESPONSES IN BIOLOGY AND MEDICINE
影响因子：
--
作者：
Akerfelt, Malin;Trouillet, Diane;Sistonen, Lea
通讯作者：
Sistonen, Lea
影响因子：
15.9
作者：
Mardach, R;Zempleni, J;Mock, DM
通讯作者：
Mock, DM