Heat shock factor protein 1

Definition:

Functions as a stress-inducible and DNA-binding transcription factor that plays a central role in the transcriptional activation of the heat shock response (HSR), leading to the expression of a large class of molecular chaperones, heat shock proteins (HSPs), that protect cells from cellular insult damage. In unstressed cells, is present in a HSP90-containing multichaperone complex that maintains it in a non-DNA-binding inactivated monomeric form. Upon exposure to heat and other stress stimuli, undergoes homotrimerization and activates HSP gene transcription through binding to site-specific heat shock elements (HSEs) present in the promoter regions of HSP genes. Upon heat shock stress, forms a chromatin-associated complex with TTC5/STRAP and p300/EP300 to stimulate HSR transcription, therefore increasing cell survival. Activation is reversible, and during the attenuation and recovery phase period of the HSR, returns to its unactivated form. Binds to inverted 5'-NGAAN-3' pentamer DNA sequences. Binds to chromatin at heat shock gene promoters. Activates transcription of transcription factor FOXR1 which in turn activates transcription of the heat shock chaperones HSPA1A and HSPA6 and the antioxidant NADPH-dependent reductase DHRS2. Also serves several other functions independently of its transcriptional activity. Involved in the repression of Ras-induced transcriptional activation of the c-fos gene in heat-stressed cells. Positively regulates pre-mRNA 3'-end processing and polyadenylation of HSP70 mRNA upon heat-stressed cells in a symplekin (SYMPK)-dependent manner. Plays a role in nuclear export of stress-induced HSP70 mRNA. Plays a role in the regulation of mitotic progression. Also plays a role as a negative regulator of non-homologous end joining (NHEJ) repair activity in a DNA damage-dependent manner. Involved in stress-induced cancer cell proliferation in a IER5-dependent manner.; (Microbial infection) Plays a role in latent human immunodeficiency virus (HIV-1) transcriptional reactivation. Binds to the HIV-1 long terminal repeat promoter (LTR) to reactivate viral transcription by recruiting cellular transcriptional elongation factors, such as CDK9, CCNT1 and EP300.

References:

[1]. Xiao-Yan Pan, et al. Heat Shock Factor 1 Mediates Latent HIV Reactivation. Sci Rep. 2016 May 18;6:26294. [Content Brief]

[2]. Danmei Xu, et al. A transcription cofactor required for the heat-shock response. EMBO Rep. 2008 Jul;9(7):662-9. [Content Brief]

[3]. Y Shi, et al. Molecular chaperones as HSF1-specific transcriptional repressors. Genes Dev. 1998 Mar 1;12(5):654-66. [Content Brief]

[4]. J Zuo, et al. Multiple layers of regulation of human heat shock transcription factor 1. Mol Cell Biol. 1995 Aug;15(8):4319-30. [Content Brief]

[5]. Ga-Young Kang, et al. Heat shock factor 1, an inhibitor of non-homologous end joining repair. Oncotarget. 2015 Oct 6;6(30):29712-24. [Content Brief]

[6]. Hollie S Skaggs, et al. HSF1-TPR interaction facilitates export of stress-induced HSP70 mRNA. J Biol Chem. 2007 Nov 23;282(47):33902-7. [Content Brief]

[7]. Hongyan Xing, et al. HSF1 modulation of Hsp70 mRNA polyadenylation via interaction with symplekin. J Biol Chem. 2004 Mar 12;279(11):10551-5. [Content Brief]

[8]. Tobias Neudegger, et al. Structure of human heat-shock transcription factor 1 in complex with DNA. Nat Struct Mol Biol. 2016 Feb;23(2):140-6. [Content Brief]

[9]. C Chen, et al. Heat shock factor 1 represses Ras-induced transcriptional activation of the c-fos gene. J Biol Chem. 1997 Oct 24;272(43):26803-6. [Content Brief]

[10]. S K Rabindran, et al. Molecular cloning and expression of a human heat shock factor, HSF1. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):6906-10. [Content Brief]

[11]. U Knauf, et al. Repression of human heat shock factor 1 activity at control temperature by phosphorylation. Genes Dev. 1996 Nov 1;10(21):2782-93. [Content Brief]

[12]. Andressa Mota, et al. FOXR1 regulates stress response pathways and is necessary for proper brain development. PLoS Genet. 2021 Nov 1;17(11):e1009854. [Content Brief]

[13]. Yoshinori Asano, et al. IER5 generates a novel hypo-phosphorylated active form of HSF1 and contributes to tumorigenesis. Sci Rep. 2016 Jan 12;6:19174. [Content Brief]

[14]. C I Holmberg, et al. Phosphorylation of serine 230 promotes inducible transcriptional activity of heat shock factor 1. EMBO J. 2001 Jul 16;20(14):3800-10. [Content Brief]

[15]. Marek A Budzyński, et al. Uncoupling Stress-Inducible Phosphorylation of Heat Shock Factor 1 from Its Activation. Mol Cell Biol. 2015 Jul;35(14):2530-40. [Content Brief]

[16]. M Green, et al. A heat shock-responsive domain of human HSF1 that regulates transcription activation domain function. Mol Cell Biol. 1995 Jun;15(6):3354-62. [Content Brief]

[17]. Yoon-Jin Lee, et al. HSF1 as a mitotic regulator: phosphorylation of HSF1 by Plk1 is essential for mitotic progression. Cancer Res. 2008 Sep 15;68(18):7550-60. [Content Brief]

[18]. C Jolly, et al. Rapid and reversible relocalization of heat shock factor 1 within seconds to nuclear stress granules. Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6769-74. [Content Brief]

[19]. Y Guo, et al. Evidence for a mechanism of repression of heat shock factor 1 transcriptional activity by a multichaperone complex. J Biol Chem. 2001 Dec 7;276(49):45791-9. [Content Brief]

[20]. W Xia, et al. Transcriptional activation of heat shock factor HSF1 probed by phosphopeptide analysis of factor 32P-labeled in vivo. J Biol Chem. 1998 Apr 10;273(15):8749-55. [Content Brief]

[21]. M P Kline, et al. Repression of the heat shock factor 1 transcriptional activation domain is modulated by constitutive phosphorylation. Mol Cell Biol. 1997 Apr;17(4):2107-15. [Content Brief]

[22]. J Zou, et al. Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1. Cell. 1998 Aug 21;94(4):471-80. [Content Brief]

[23]. Frank Boellmann, et al. DAXX interacts with heat shock factor 1 during stress activation and enhances its transcriptional activity. Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4100-5. [Content Brief]

[24]. K Abravaya, et al. Heat shock-induced interactions of heat shock transcription factor and the human hsp70 promoter examined by in vivo footprinting. Mol Cell Biol. 1991 Jan;11(1):586-92. [Content Brief]

[25]. Fabrice Soncin, et al. Transcriptional activity and DNA binding of heat shock factor-1 involve phosphorylation on threonine 142 by CK2. Biochem Biophys Res Commun. 2003 Apr 4;303(2):700-6. [Content Brief]

[26]. XiaoZhe Wang, et al. Phosphorylation of HSF1 by MAPK-activated protein kinase 2 on serine 121, inhibits transcriptional activity and promotes HSP90 binding. J Biol Chem. 2006 Jan 13;281(2):782-91. [Content Brief]

[27]. R Baler, et al. Activation of human heat shock genes is accompanied by oligomerization, modification, and rapid translocation of heat shock transcription factor HSF1. Mol Cell Biol. 1993 Apr;13(4):2486-96. [Content Brief]

[28]. B Chu, et al. Sequential phosphorylation by mitogen-activated protein kinase and glycogen synthase kinase 3 represses transcriptional activation by heat shock factor-1. J Biol Chem. 1996 Nov 29;271(48):30847-57. [Content Brief]

[29]. XiaoZhe Wang, et al. Regulation of molecular chaperone gene transcription involves the serine phosphorylation, 14-3-3 epsilon binding, and cytoplasmic sequestration of heat shock factor 1. Mol Cell Biol. 2003 Sep;23(17):6013-26. [Content Brief]

[30]. J Zuo, et al. Activation of the DNA-binding ability of human heat shock transcription factor 1 may involve the transition from an intramolecular to an intermolecular triple-stranded coiled-coil structure. Mol Cell Biol. 1994 Nov;14(11):7557-68. [Content Brief]

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