Ser326
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Home > Phosphorylation Site Page: > Ser326  -  HSF1 (human)

Site Information
ssVDtLLsPTALIDs   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 455484

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 55 ) , electrophoretic mobility shift ( 48 ) , immunoassay ( 5 , 37 , 41 , 44 ) , immunoprecipitation ( 14 , 22 , 29 , 36 , 39 , 46 ) , mass spectrometry ( 9 , 13 , 22 , 25 , 27 , 36 , 40 , 42 , 47 , 50 , 51 , 52 , 53 , 54 , 55 ) , mass spectrometry (in vitro) ( 4 , 9 , 49 ) , mutation of modification site ( 4 , 5 , 9 , 10 , 13 , 16 , 22 , 33 , 35 , 36 , 43 , 46 , 48 , 55 ) , peptide sequencing ( 55 ) , phospho-antibody ( 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 21 , 22 , 23 , 24 , 26 , 28 , 29 , 30 , 31 , 32 , 34 , 35 , 36 , 37 , 38 , 43 , 44 , 45 , 48 , 49 , 55 ) , western blotting ( 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 20 , 21 , 22 , 23 , 24 , 26 , 28 , 29 , 30 , 31 , 32 , 34 , 35 , 36 , 37 , 38 , 39 , 43 , 44 , 45 , 46 , 48 , 49 )
Disease tissue studied:
bone cancer ( 12 , 30 ) , breast cancer ( 9 , 14 , 15 , 16 , 20 , 22 , 26 , 27 , 34 , 37 , 42 , 46 ) , breast adenocarcinoma ( 9 , 14 , 15 ) , breast ductal carcinoma ( 42 ) , HER2 positive breast cancer ( 25 ) , luminal A breast cancer ( 25 ) , luminal B breast cancer ( 25 ) , breast cancer, triple negative ( 9 , 14 , 15 , 25 ) , cervical cancer ( 50 ) , cervical adenocarcinoma ( 50 ) , colorectal cancer ( 18 , 32 ) , colorectal carcinoma ( 18 , 32 ) , endometrial cancer ( 19 ) , endometrial adenocarcinoma ( 19 ) , gallbladder cancer ( 8 ) , liver cancer ( 29 ) , lung cancer ( 21 , 26 , 31 , 43 , 44 ) , non-small cell lung cancer ( 21 , 26 , 31 , 43 , 44 ) , non-small cell lung adenocarcinoma ( 26 , 44 ) , non-small cell large cell lung carcinoma ( 21 , 31 , 43 ) , lymphoma ( 38 , 45 ) , B cell lymphoma ( 38 ) , non-Hodgkin's lymphoma ( 38 ) , mantle cell lymphoma ( 38 ) , ovarian cancer ( 19 , 28 , 34 , 42 ) , multiple myeloma ( 17 , 23 ) , prostate cancer ( 45 )
Relevant cell line - cell type - tissue:
293 (epithelial) ( 4 , 10 ) , A431 (epithelial) ( 22 ) , A549 (pulmonary) ( 26 , 44 ) , brain ( 39 ) , breast ( 25 , 37 , 42 ) , BT-20 (breast cell) ( 15 ) , BT-474 (breast cell) ( 15 , 16 , 20 , 26 , 37 ) , BT-549 (breast cell) ( 15 ) , CGL2 (fibroblast) ( 5 , 48 ) , epithelial-corneal ( 3 ) , GM05659 (fibroblast) ( 24 ) , GM18453 (fibroblast) ( 24 ) , HCT116 (intestinal) ( 18 , 32 ) , HEC-1B (endometrial) ( 19 ) , HEK293T (epithelial) ( 9 , 48 ) , HeLa (cervical) ( 6 , 30 , 33 , 40 , 46 , 48 , 49 , 51 , 54 , 55 ) , HeLa S3 (cervical) ( 50 ) , HepG2 (hepatic) ( 29 ) , HEY (ovarian) ( 28 ) , HFF1 (fibroblast) ( 44 ) , HTBoA (ovarian) ( 19 ) , IMR-90 (fibroblast) ( 21 ) , JEKO-1 (B lymphocyte) ( 38 ) , Jurkat (T lymphocyte) ( 47 , 52 ) , K562 (erythroid) ( 53 ) , KMS-18 (B lymphocyte) ( 23 ) , lymphocyte ( 10 ) , MCAS (ovarian) ( 19 ) , MCF-10A (breast cell) ( 34 ) , MCF-7 (breast cell) ( 14 , 15 , 16 , 20 , 27 , 34 , 37 , 46 ) , MCF10A1 (epithelial) ( 7 , 14 ) , MCF12A (epithelial) ( 14 ) , MDA-MB-231 (breast cell) ( 16 , 22 , 34 , 37 ) , MDA-MB-468 (breast cell) ( 9 , 14 , 15 ) , MEF (fibroblast) ( 13 , 33 , 43 ) , MM1.S (lymphoblast) ( 17 , 23 ) , monocyte-blood ( 2 , 41 ) , mononuclear-blood ( 2 ) , myoblast ( 10 ) , NCI-H460 (pulmonary) ( 21 , 31 , 43 ) , NCI-H929 (B lymphocyte) ( 17 ) , NOZ ('epithelial, gallbladder') ( 8 ) , ovary ( 42 ) , PC3 (prostate cell) ( 45 ) , RAW 264.7 (macrophage) ( 41 ) , rectal gland tubules ( 39 ) , RKO (intestinal) ( 32 ) , RPMI-8266 (plasma cell) ( 23 ) , SD1 (lymphoblastoid) ( 8 ) , SKBr3 (breast cell) ( 14 , 15 , 26 ) , SKOV-3 (ovarian) ( 28 , 34 ) , SMMC7721 (hepatocyte) ( 29 ) , T47D (breast cell) ( 14 , 15 ) , U-937 (myeloid) ( 45 ) , U266 (plasma cell) ( 17 , 23 ) , U2OS (bone cell) ( 12 , 30 ) , Z138 (B lymphocyte) ( 38 )

Upstream Regulation
Regulatory protein:
Akt2 (human) ( 4 ) , Akt3 (human) ( 4 ) , ER-alpha (human) ( 14 ) , HER2 (human) ( 37 ) , HRas (human) ( 7 ) , HSF2 (human) ( 12 ) , THBS4 (human) ( 8 )
Putative in vivo kinases:
Akt1 (human) ( 4 , 8 , 37 ) , DYRK2 (human) ( 4 , 6 , 9 ) , ERK1 (human) ( 35 ) , ERK2 (human) ( 35 ) , MEK1 (human) ( 4 , 36 ) , mTOR (human) ( 4 , 34 , 49 ) , P38A (human) ( 4 ) , P38G (human) ( 22 )
Kinases, in vitro:
Akt1 (human) ( 4 , 37 ) , Akt2 (human) ( 4 ) , DYRK2 (human) ( 4 , 9 ) , MEK1 (human) ( 4 , 36 ) , mTOR (human) ( 4 , 49 ) , P38A (human) ( 4 , 22 ) , P38B (human) ( 22 ) , P38D (human) ( 22 ) , P38G (human) ( 22 )
Treatments:
17-beta-estradiol ( 14 ) , 1Na-PP1 ( 9 ) , 1NM-PP1 ( 9 ) , 2,4-Bis(4-hydroxybenzyl)phenol ( 43 ) , 3-MB-PP1 ( 9 ) , 4-HT ( 14 ) , antibody ( 8 , 52 ) , arsenite ( 49 ) , As2O3 ( 5 , 48 ) , BIRB-0796 ( 22 ) , bisphenol_A ( 14 ) , bleomycin ( 21 ) , bortezomib ( 12 , 17 , 23 ) , carbendazim ( 32 ) , carfilzomib ( 17 ) , Cd(2+) ( 49 ) , celastrol ( 26 , 45 ) , Coniferyl aldehyde ( 35 ) , CPT ( 21 ) , cycloheximide ( 43 ) , ethanol ( 41 ) , faslodex ( 14 ) , fenbendazole ( 32 ) , formaldehyde ( 21 ) , geldanamycin ( 26 ) , glucose ( 29 ) , glucose_starvation ( 29 ) , harmine ( 9 ) , heat_shock ( 2 , 7 , 9 , 20 , 28 , 29 , 30 , 31 , 39 , 41 , 44 , 49 , 55 ) , heating ( 4 , 24 , 48 ) , heregulin ( 37 ) , hydroxyurea ( 21 ) , injury ( 3 ) , ischemia ( 42 ) , JNK_inhibitor_VIII ( 22 ) , KPT-185 ( 38 ) , KRIBB11 ( 7 ) , KU-0063794 ( 49 ) , lapatinib ( 20 , 37 ) , LPS ( 41 ) , LY294002 ( 8 , 14 , 37 , 48 ) , mebendazole ( 32 ) , MG132 ( 12 , 21 , 49 ) , MK-2206 ( 4 ) , mutation ( 39 ) , nocodazole ( 32 , 50 ) , novobiocin ( 45 ) , NU7026 ( 48 ) , NVP-AUY922 ( 15 ) , oxfendazole ( 32 ) , parbendazole ( 32 ) , PD98059 ( 48 ) , PEITC ( 22 ) , PI-103 ( 48 ) , piR-823 ( 18 ) , PPT ( 14 ) , rapamycin ( 4 , 9 , 14 , 29 , 48 , 49 ) , SB202190 ( 9 ) , SCH772984 ( 7 ) , selumetinib ( 7 , 36 ) , siRNA ( 4 , 9 , 34 , 37 , 49 ) , staurosporine ( 49 ) , tanespimycin ( 45 , 49 ) , taxol ( 5 ) , TG02 ( 17 ) , TPEN ( 2 ) , U0126 ( 14 , 22 , 32 , 35 , 36 ) , vinblastine ( 5 ) , virus infection ( 44 ) , X66 ( 26 ) , Zn(2+) ( 2 )

Downstream Regulation
Effects of modification on HSF1:
activity, induced ( 4 , 16 , 36 , 44 , 55 ) , enzymatic activity, induced ( 16 ) , intracellular localization ( 8 , 36 , 44 ) , molecular association, regulation ( 4 , 13 , 18 ) , phosphorylation ( 34 ) , protein conformation ( 22 ) , protein stabilization ( 7 , 9 , 20 , 35 , 36 , 43 )
Effects of modification on biological processes:
apoptosis, inhibited ( 2 , 9 , 48 ) , carcinogenesis, altered ( 29 ) , carcinogenesis, induced ( 7 , 8 , 9 , 37 ) , cell cycle regulation ( 5 ) , cell differentiation, induced ( 8 ) , cell growth, induced ( 3 , 5 , 8 , 16 ) , cell motility, induced ( 3 ) , cytoskeletal reorganization ( 5 ) , signaling pathway regulation ( 8 , 37 ) , transcription, altered ( 10 , 55 ) , transcription, induced ( 2 , 3 , 4 , 5 , 8 , 9 , 13 , 14 , 15 , 19 , 20 , 22 , 29 , 34 , 35 , 36 , 37 , 44 , 46 , 48 , 49 ) , transcription, inhibited ( 33 ) , translation, altered ( 10 ) , translation, induced ( 34 )
Induce interaction with:
CDK9 (human) ( 4 ) , GTF2B (human) ( 4 ) , PIN1 (human) ( 46 ) , RNA ( 18 ) , SGOL2 (human) ( 13 )

Disease / Diagnostics Relevance
Relevant diseases:
breast cancer ( 37 ) , acute myelogenous leukemia ( 10 ) , ovarian cancer ( 19 )

References 

1

Jacobs C, et al. (2023) HSF1 inhibits antitumor immune activity in breast cancer by suppressing CCL5 to block CD8+ T cell recruitment. Cancer Res
37890164   Curated Info

2

Peng-Winkler Y, Büttgenbach A, Rink L, Wessels I (2022) Zinc supplementation prior to heat shock enhances HSP70 synthesis through HSF1 phosphorylation at serine 326 in human peripheral mononuclear cells. Food Funct 13, 9143-9152
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3

Wang M, et al. (2022) The Therapeutic Roles of Recombinant Hsp90α on Cornea Epithelial Injury. Invest Ophthalmol Vis Sci 63, 30
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4

Lu WC, et al. (2022) AKT1 mediates multiple phosphorylation events that functionally promote HSF1 activation. FEBS J
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5

Kuo HH, Su ZR, Chuang JY, Yih LH (2021) Heat shock factor 1 suppression induces spindle abnormalities and sensitizes cells to antimitotic drugs. Cell Div 16, 8
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6

Lara-Chica M, et al. (2021) A novel CDC25A/DYRK2 regulatory switch modulates cell cycle and survival. Cell Death Differ 29
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7

Tervonen TA, et al. (2021) Oncogenic Ras disrupts epithelial integrity by activating the transmembrane serine protease hepsin. Cancer Res
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8

Shi Y, et al. (2021) Thrombospondin 4/integrin α2/HSF1 axis promotes proliferation and cancer stem-like traits of gallbladder cancer by enhancing reciprocal crosstalk between cancer-associated fibroblasts and tumor cells. J Exp Clin Cancer Res 40, 14
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9

Moreno R, et al. (2020) The stress-responsive kinase DYRK2 activates heat shock factor 1 promoting resistance to proteotoxic stress. Cell Death Differ
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10

Hoff FW, et al. (2020) Heat Shock Factor 1 (HSF1-pSer326) Predicts Response to Bortezomib-Containing Chemotherapy in Pediatric AML: A COG Study. Blood
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11

Mun GI, Choi E, Lee Y, Lee YS (2020) Decreased expression of FBXW7 by ERK1/2 activation in drug-resistant cancer cells confers transcriptional activation of MDR1 by suppression of ubiquitin degradation of HSF1. Cell Death Dis
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12

Joutsen J, et al. (2020) Heat Shock Factor 2 Protects against Proteotoxicity by Maintaining Cell-Cell Adhesion. Cell Rep 30, 583-597.e6
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13

Takii R, et al. (2019) The pericentromeric protein shugoshin 2 cooperates with HSF1 in heat shock response and RNA Pol II recruitment. EMBO J, e102566
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14

Vydra N, et al. (2019) 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel) 11
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15

Pastorek M, Muller P, Coates PJ, Vojtesek B (2018) Intrinsic proteotoxic stress levels vary and act as a predictive marker for sensitivity of cancer cells to Hsp90 inhibition. PLoS One 13, e0202758
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16

Carpenter RL, et al. (2017) Combined inhibition of AKT and HSF1 suppresses breast cancer stem cells and tumor growth. Oncotarget 8, 73947-73963
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17

Shah SP, Nooka AK, Lonial S, Boise LH (2017) TG02 inhibits proteasome inhibitor-induced HSF1 serine 326 phosphorylation and heat shock response in multiple myeloma. Blood Adv 1, 1848-1853
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18

Yin J, et al. (2017) piR-823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF1. Cancer Sci 108, 1746-1756
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19

Yasuda K, et al. (2017) Phosphorylation of HSF1 at serine 326 residue is related to the maintenance of gynecologic cancer stem cells through expression of HSP27. Oncotarget 8, 31540-31553
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20

Li D, Marchenko ND (2017) ErbB2 inhibition by lapatinib promotes degradation of mutant p53 protein in cancer cells. Oncotarget 8, 5823-5833
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21

Ortega-Atienza S, Rubis B, McCarthy C, Zhitkovich A (2016) Formaldehyde Is a Potent Proteotoxic Stressor Causing Rapid Heat Shock Transcription Factor 1 Activation and Lys48-Linked Polyubiquitination of Proteins. Am J Pathol 186, 2857-2868
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22

Dayalan Naidu S, et al. (2016) Heat Shock Factor 1 Is a Substrate for p38 Mitogen-Activated Protein Kinases. Mol Cell Biol 36, 2403-17
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23

Shah SP, et al. (2016) Bortezomib-induced heat shock response protects multiple myeloma cells and is activated by heat shock factor 1 serine 326 phosphorylation. Oncotarget 7, 59727-59741
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24

Kirkegaard T, et al. (2016) Heat shock protein-based therapy as a potential candidate for treating the sphingolipidoses. Sci Transl Med 8, 355ra118
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25

Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62
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26

Zhao Z, et al. (2016) X66, a novel N-terminal heat shock protein 90 inhibitor, exerts antitumor effects without induction of heat shock response. Oncotarget 7, 29648-63
27105490   Curated Info

27

Carrier M, et al. (2016) Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines. PLoS One 11, e0157290
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28

Powell CD, et al. (2016) The Heat Shock Transcription Factor HSF1 Induces Ovarian Cancer Epithelial-Mesenchymal Transition in a 3D Spheroid Growth Model. PLoS One 11, e0168389
27997575   Curated Info

29

Ma W, et al. (2015) Glucose regulates heat shock factor 1 transcription activity via mTOR pathway in HCC cell lines. Cell Biol Int 39, 1217-24
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30

Sun X, et al. (2015) HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene 34, 5617-25
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31

Kang GY, et al. (2015) Heat shock factor 1, an inhibitor of non-homologous end joining repair. Oncotarget 6, 29712-24
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32

Wales CT, et al. (2015) ERK-dependent phosphorylation of HSF1 mediates chemotherapeutic resistance to benzimidazole carbamates in colorectal cancer cells. Anticancer Drugs 26, 657-66
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33

Budzyński MA, Puustinen MC, Joutsen J, Sistonen L (2015) Uncoupling Stress-Inducible Phosphorylation of Heat Shock Factor 1 from Its Activation. Mol Cell Biol 35, 2530-40
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34

Chou SD, et al. (2015) HSF1 regulation of β-catenin in mammary cancer cells through control of HuR/elavL1 expression. Oncogene 34, 2178-88
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35

Kim SY, et al. (2015) Coniferyl aldehyde reduces radiation damage through increased protein stability of heat shock transcriptional factor 1 by phosphorylation. Int J Radiat Oncol Biol Phys 91, 807-16
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36

Tang Z, et al. (2015) MEK Guards Proteome Stability and Inhibits Tumor-Suppressive Amyloidogenesis via HSF1. Cell 160, 729-44
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37

Carpenter RL, Paw I, Dewhirst MW, Lo HW (2015) Akt phosphorylates and activates HSF-1 independent of heat shock, leading to Slug overexpression and epithelial-mesenchymal transition (EMT) of HER2-overexpressing breast cancer cells. Oncogene 34, 546-57
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38

Tabe Y, et al. (2015) Ribosomal Biogenesis and Translational Flux Inhibition by the Selective Inhibitor of Nuclear Export (SINE) XPO1 Antagonist KPT-185. PLoS One 10, e0137210
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39

Roth DM, et al. (2014) Modulation of the maladaptive stress response to manage diseases of protein folding. PLoS Biol 12, e1001998
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40

Sharma K, et al. (2014) Ultradeep human phosphoproteome reveals a distinct regulatory nature of Tyr and Ser/Thr-based signaling. Cell Rep 8, 1583-94
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41

Muralidharan S, et al. (2014) Moderate Alcohol Induces Stress Proteins HSF1 and hsp70 and Inhibits Proinflammatory Cytokines Resulting in Endotoxin Tolerance. J Immunol 193, 1975-87
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42

Mertins P, et al. (2014) Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels. Mol Cell Proteomics 13, 1690-704
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43

Yoon T, et al. (2014) 2,4-Bis(4-hydroxybenzyl)phenol Inhibits Heat Shock Transcription Factor 1 and Sensitizes Lung Cancer Cells to Conventional Anticancer Modalities. J Nat Prod 77, 1123-1129
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44

Filone CM, et al. (2014) The master regulator of the cellular stress response (HSF1) is critical for orthopoxvirus infection. PLoS Pathog 10, e1003904
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45

Peng B, et al. (2014) Peptide deformylase inhibitor actinonin reduces celastrol's HSP70 induction while synergizing proliferation inhibition in tumor cells. BMC Cancer 14, 146
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46

Wang HY, Fu JC, Lee YC, Lu PJ (2013) Hyperthermia Stress Activates Heat Shock Protein Expression via Propyl Isomerase 1 Regulation with Heat Shock Factor 1. Mol Cell Biol 33, 4889-99
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47

Mertins P, et al. (2013) Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods 10, 634-7
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48

Yih LH, Hsu NC, Kuo HH, Wu YC (2012) Inhibition of the heat shock response by PI103 enhances the cytotoxicity of arsenic trioxide. Toxicol Sci 128, 126-36
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49

Chou SD, Prince T, Gong J, Calderwood SK (2012) mTOR Is Essential for the Proteotoxic Stress Response, HSF1 Activation and Heat Shock Protein Synthesis. PLoS One 7, e39679
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50

Olsen JV, et al. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3, ra3
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51

Chen RQ, et al. (2009) CDC25B mediates rapamycin-induced oncogenic responses in cancer cells. Cancer Res 69, 2663-8
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52

Mayya V, et al. (2009) Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal 2, ra46
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53

Stokes M (2008) CST Curation Set: 4605; Year: 2008; Biosample/Treatment: cell line, K562/untreated; Disease: chronic myelogenous leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[STY])
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54

Cantin GT, et al. (2008) Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res 7, 1346-51
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55

Guettouche T, Boellmann F, Lane WS, Voellmy R (2005) Analysis of phosphorylation of human heat shock factor 1 in cells experiencing a stress. BMC Biochem 6, 4
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