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 ( 41 ) , immunoprecipitation ( 8 , 15 , 22 , 32 ) , mass spectrometry ( 8 , 11 , 13 , 22 , 26 , 28 , 33 , 36 , 37 , 38 , 39 , 40 , 41 ) , mutation of modification site ( 2 , 8 , 19 , 22 , 32 , 41 ) , peptide sequencing ( 41 ) , phospho-antibody ( 2 , 3 , 4 , 7 , 8 , 9 , 10 , 12 , 14 , 15 , 16 , 17 , 18 , 22 , 24 , 41 ) , western blotting ( 2 , 3 , 4 , 7 , 8 , 9 , 10 , 12 , 14 , 15 , 16 , 17 , 18 , 22 , 24 , 32 )
Disease tissue studied:
bone cancer ( 16 ) , breast cancer ( 2 , 8 , 12 , 13 , 28 , 32 ) , breast ductal carcinoma ( 28 ) , HER2 positive breast cancer ( 11 ) , luminal A breast cancer ( 11 ) , luminal B breast cancer ( 11 ) , breast cancer, triple negative ( 11 ) , cervical cancer ( 36 ) , cervical adenocarcinoma ( 36 ) , colorectal cancer ( 4 , 18 ) , colorectal carcinoma ( 4 , 18 ) , endometrial cancer ( 5 ) , endometrial adenocarcinoma ( 5 ) , liver cancer ( 15 ) , lung cancer ( 7 , 12 , 17 ) , non-small cell lung cancer ( 7 , 12 , 17 ) , non-small cell lung adenocarcinoma ( 12 ) , non-small cell large cell lung carcinoma ( 7 , 17 ) , lymphoma ( 24 ) , B cell lymphoma ( 24 ) , non-Hodgkin's lymphoma ( 24 ) , mantle cell lymphoma ( 24 ) , ovarian cancer ( 5 , 14 , 28 ) , multiple myeloma ( 3 , 9 )
Relevant cell line - cell type - tissue:
A431 (epithelial) ( 8 ) , A549 (pulmonary) ( 12 ) , breast ( 11 , 28 ) , BT-474 (breast cell) ( 2 , 12 ) , GM05659 (fibroblast) ( 10 ) , GM18453 (fibroblast) ( 10 ) , HCT116 (intestinal) ( 4 , 18 ) , HEC-1B (endometrial) ( 5 ) , HeLa (cervical) ( 16 , 19 , 26 , 32 , 37 , 40 , 41 ) , HeLa S3 (cervical) ( 36 ) , HepG2 (hepatic) ( 15 ) , HEY (ovarian) ( 14 ) , HTBoA (ovarian) ( 5 ) , IMR-90 (fibroblast) ( 7 ) , JEKO-1 (B lymphocyte) ( 24 ) , Jurkat (T lymphocyte) ( 33 , 38 ) , K562 (erythroid) ( 39 ) , KMS-18 (B lymphocyte) ( 9 ) , MCAS (ovarian) ( 5 ) , MCF-7 (breast cell) ( 2 , 13 , 32 ) , MDA-MB-231 (breast cell) ( 2 , 8 ) , MEF (fibroblast) ( 19 ) , MM.1S (lymphoblast) ( 3 , 9 ) , NCI-H460 (pulmonary) ( 7 , 17 ) , NCI-H929 (B lymphocyte) ( 3 ) , ovary ( 28 ) , RKO (intestinal) ( 18 ) , RPMI-8226 (plasma cell) ( 9 ) , SKBr3 (breast cell) ( 12 ) , SKOV-3 (ovarian) ( 14 ) , SMMC7721 (hepatocyte) ( 15 ) , U266 (plasma cell) ( 3 , 9 ) , U2OS (bone cell) ( 16 ) , Z138 (B lymphocyte) ( 24 )

Upstream Regulation
Putative in vivo kinases:
MEK1 (human) ( 22 ) , mTOR (human) ( 35 ) , P38G (human) ( 8 )
Kinases, in vitro:
MEK1 (human) ( 22 ) , P38A (human) ( 8 ) , P38B (human) ( 8 ) , P38D (human) ( 8 ) , P38G (human) ( 8 )
Treatments:
anti-CD3 ( 38 ) , arsenite ( 35 ) , BIRB-0796 ( 8 ) , bleomycin ( 7 ) , bortezomib ( 3 , 9 ) , carbendazim ( 18 ) , carfilzomib ( 3 ) , celastrol ( 12 ) , CPT ( 7 ) , fenbendazole ( 18 ) , formaldehyde ( 7 ) , geldanamycin ( 12 ) , glucose ( 15 ) , glucose_starvation ( 15 ) , heat_shock ( 14 , 15 , 16 , 17 , 35 , 41 ) , heating ( 10 ) , hydroxyurea ( 7 ) , ischemia ( 28 ) , JNK_inhibitor_VIII ( 8 ) , KPT-185 ( 24 ) , mebendazole ( 18 ) , MG132 ( 7 , 35 ) , nocodazole ( 18 , 36 ) , oxfendazole ( 18 ) , parbendazole ( 18 ) , PEITC ( 8 ) , piR-823 ( 4 ) , rapamycin ( 15 , 35 ) , selumetinib ( 22 ) , staurosporine ( 35 ) , TG02 ( 3 ) , U0126 ( 8 , 18 , 22 ) , X66 ( 12 )

Downstream Regulation
Effects of modification on HSF1:
activity, induced ( 2 , 22 , 41 ) , enzymatic activity, induced ( 2 ) , intracellular localization ( 22 ) , molecular association, regulation ( 4 ) , protein conformation ( 8 ) , protein stabilization ( 22 )
Effects of modification on biological processes:
carcinogenesis, altered ( 15 ) , cell growth, induced ( 2 ) , transcription, altered ( 41 ) , transcription, induced ( 5 , 8 , 15 , 20 , 22 , 23 , 32 , 34 , 35 ) , transcription, inhibited ( 19 )
Induce interaction with:
PIN1 (human) ( 32 ) , RNA ( 4 )

Disease / Diagnostics Relevance
Relevant diseases:
ovarian cancer ( 5 )

References 

1

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
30138434   Curated Info

2

Carpenter RL, et al. (2017) Combined inhibition of AKT and HSF1 suppresses breast cancer stem cells and tumor growth. Oncotarget 8, 73947-73963
29088759   Curated Info

3

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
29296831   Curated Info

4

Yin J, et al. (2017) piR-823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF1. Cancer Sci 108, 1746-1756
28618124   Curated Info

5

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
28415561   Curated Info

6

Li D, Marchenko ND (2017) ErbB2 inhibition by lapatinib promotes degradation of mutant p53 protein in cancer cells. Oncotarget 8, 5823-5833
27791982   Curated Info

7

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
27639166   Curated Info

8

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
27354066   Curated Info

9

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
27487129   Curated Info

10

Kirkegaard T, et al. (2016) Heat shock protein-based therapy as a potential candidate for treating the sphingolipidoses. Sci Transl Med 8, 355ra118
27605553   Curated Info

11

Mertins P, et al. (2016) Proteogenomics connects somatic mutations to signalling in breast cancer. Nature 534, 55-62
27251275   Curated Info

12

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

13

Carrier M, et al. (2016) Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines. PLoS One 11, e0157290
27362937   Curated Info

14

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

15

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
26010766   Curated Info

16

Sun X, et al. (2015) HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene 34, 5617-25
25728673   Curated Info

17

Kang GY, et al. (2015) Heat shock factor 1, an inhibitor of non-homologous end joining repair. Oncotarget 6, 29712-24
26359349   Curated Info

18

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
25811962   Curated Info

19

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
25963659   Curated Info

20

Chou SD, et al. (2015) HSF1 regulation of β-catenin in mammary cancer cells through control of HuR/elavL1 expression. Oncogene 34, 2178-88
24954509   Curated Info

21

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
25752395   Curated Info

22

Tang Z, et al. (2015) MEK Guards Proteome Stability and Inhibits Tumor-Suppressive Amyloidogenesis via HSF1. Cell 160, 729-44
25679764   Curated Info

23

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
24469056   Curated Info

24

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
26340096   Curated Info

25

Roth DM, et al. (2014) Modulation of the maladaptive stress response to manage diseases of protein folding. PLoS Biol 12, e1001998
25406061   Curated Info

26

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
25159151   Curated Info

27

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
25024384   Curated Info

28

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
24719451   Curated Info

29

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
24746225   Curated Info

30

Filone CM, et al. (2014) The master regulator of the cellular stress response (HSF1) is critical for orthopoxvirus infection. PLoS Pathog 10, e1003904
24516381   Curated Info

31

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
24589236   Curated Info

32

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
24126052   Curated Info

33

Mertins P, et al. (2013) Integrated proteomic analysis of post-translational modifications by serial enrichment. Nat Methods 10, 634-7
23749302   Curated Info

34

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
22496356   Curated Info

35

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
22768106   Curated Info

36

Olsen JV, et al. (2010) Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal 3, ra3
20068231   Curated Info

37

Chen RQ, et al. (2009) CDC25B mediates rapamycin-induced oncogenic responses in cancer cells. Cancer Res 69, 2663-8
19276368   Curated Info

38

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
19690332   Curated Info

39

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])
Curated Info

40

Cantin GT, et al. (2008) Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res 7, 1346-51
18220336   Curated Info

41

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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