Coactivators necessary for transcriptional output of the hypoxia inducible factor, HIF, are directly recruited by ARNT PAS-B

Carrie L Partch; Kevin H. Gardner

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Coactivators necessary for transcriptional output of the hypoxia inducible factor, HIF, are directly recruited by ARNT PAS-B

机译：缺氧诱导因子HIF转录输出所必需的共激活因子由ARNT PAS-B直接募集

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Hypoxia-inducible factor (HIF) is the key transcriptional effector of the hypoxia response in eukaryotes, coordinating the expression of genes involved in oxygen transport, glycolysis, and angiogenesis to promote adaptation to low oxygen levels. HIF is a basic helix-loop-helix (bHLH)-PAS (PER-ARNT-SIM) heterodimer composed of an oxygen-labile HIF-a subunit and a constitutively expressed aryl hydrocarbon receptor nuclear translocator (ARNT) subunit, which dimerize via basic helix-loop-helix and PAS domains, and recruit coactivators via HIF-a C-terminal transactivation domains. Here we demonstrate that the ARNT PAS-B domain provides an additional recruitment site by binding the coactivator transforming acidic coiled-coil 3 (TACC3) in a step necessary for transcriptional responses to hypoxia. Structural insights from NMR spectroscopy illustrate how this PAS domain simultaneously mediates interactions with HIF-a and TACC3. Finally, mutations on ARNT PAS-B modulate coactivator selectivity and target gene induction by HIF in vivo, demonstrating a bifunctionaf role for transcriptional regulation by PAS domains within bHLH-PAS transcription factors.

机译：缺氧诱导因子（HIF）是真核生物中缺氧反应的关键转录效应因子，可协调参与氧转运，糖酵解和血管生成的基因的表达，从而促进对低氧水平的适应。 HIF是一种基本的螺旋-环-螺旋（bHLH）-PAS（PER-ARNT-SIM）异二聚体，它由氧不稳定的HIF-a亚基和组成性表达的芳烃受体核转运子（ARNT）亚基组成，它们通过碱性二聚螺旋-环-螺旋和PAS域，并通过HIF-αC末端反式激活域募集共激活因子。在这里，我们证明了ARNT PAS-B域通过在对缺氧的转录反应所必需的步骤中结合共激活因子转化酸性卷曲螺旋3（TACC3）提供了一个额外的募集位点。 NMR光谱的结构见解说明了该PAS域如何同时介导与HIF-a和TACC3的相互作用。最后，ARNT PAS-B上的突变可在体内通过HIF调节共激活因子的选择性和靶基因的诱导，证明bHLH-PAS转录因子内PAS域的转录调控具有双重功能。

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《Proceedings of the National Academy of Sciences of the United States of America》 |2011年第19期|p.7739-7744|共6页
作者
Carrie L Partch; Kevin H. Gardner;
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作者单位

Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-8816;

Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-8816;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种 eng
中图分类
关键词
transcriptional coactivators; protein/protein interactions; bifunctional interactions;

机译：转录共激活因子;蛋白质/蛋白质相互作用;双功能相互作用;

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机译：缺氧诱导因子（HIF）-1α直接响应缺氧和表皮生长因子（EGF）增强干细胞因子（SCF）的转录活性。
2. Hypoxia-inducible factor (HIF)-1α directly enhances the transcriptional activity of stem cell factor (SCF) in response to hypoxia and epidermal growth factor (EGF) [J] . Zhi-Bo Han13? He Ren13? Hui Zhao23? Ying Chi13 Ke Chen13 Bin Zhou1 Yong-jun Liu123 Lei Zhang1 Bin Xu123 Bin Liu1 Renchi Yang1 and Zhong-Chao Han123 Carcinogenesis . 2008,第10期

机译：缺氧诱导因子（HIF）-1α响应缺氧和表皮生长因子（EGF）直接增强干细胞因子（SCF）的转录活性
3. Expression of the forkhead transcription factor FOXP1 is associated both with hypoxia inducible factors (HIFs) and the androgen receptor in prostate cancer but is not directly regulated by androgens or hypoxia. [J] . Banham AH, Boddy J, Launchbury R, The Prostate . 2007,第10期

机译：前叉转录因子FOXP1的表达与低氧诱导因子（HIF）和前列腺癌中的雄激素受体相关，但不受雄激素或低氧的直接调节。
4. Hypoxia inducible factor-la (HIF-1α) stabilization for enhanced cell and tissue construct survival [C] . Wai Ho, Barry Fuller, Gavin Jell European conference on biomaterials . 2014

机译：缺氧诱导因子-la（HIF-1α）稳定化可增强细胞和组织构建体的存活率
5. Identification and Characterisation of the Post-translational Modifications that Regulate the Hypoxia Inducible Factors, HIF-1α and HIF-2α [D] . ?Daly, Leonard 2020

机译：调节缺氧诱导因子，HIF-1α和HIF-2α的翻译后修饰的鉴定和表征。
6. Coactivators necessary for transcriptional output of the hypoxia inducible factor HIF are directly recruited by ARNT PAS-B [O] . Carrie L. Partch, Kevin H. Gardner 2011

机译：缺氧诱导因子HIF转录输出所必需的共激活因子由ARNT PAS-B直接募集
7. Coactivators necessary for transcriptional output of the hypoxia inducible factor, HIF, are directly recruited by ARNT PAS-B [O] . Partch, Carrie L., Gardner, Kevin H. 2011

机译：缺氧诱导因子HIF转录输出所必需的共激活因子由ARNT PAS-B直接募集

Coactivators necessary for transcriptional output of the hypoxia inducible factor, HIF, are directly recruited by ARNT PAS-B

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