Ser307
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Home > Phosphorylation Site Page: > Ser307  -  HSF1 (human)

Site Information
EPPsPPQsPRVEEAs   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 449046

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 53 ) , [32P] bio-synthetic labeling ( 48 , 51 ) , electrophoretic mobility shift ( 54 ) , immunoprecipitation ( 2 , 5 , 11 , 54 ) , mass spectrometry ( 2 , 4 , 6 , 7 , 9 , 10 , 11 , 13 , 14 , 15 , 16 , 18 , 19 , 21 , 23 , 24 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 48 , 49 ) , mutation of modification site ( 2 , 5 , 8 , 11 , 12 , 46 , 50 , 52 , 53 , 54 ) , peptide sequencing ( 48 ) , phospho-antibody ( 2 , 3 , 5 , 11 , 34 , 46 , 50 , 51 ) , phosphopeptide mapping ( 51 , 54 ) , western blotting ( 2 , 3 , 5 , 11 , 34 , 46 , 52 , 53 , 54 )
Disease tissue studied:
bone cancer ( 46 ) , breast cancer ( 2 , 6 , 15 , 16 ) , breast ductal carcinoma ( 15 ) , HER2 positive breast cancer ( 4 ) , luminal A breast cancer ( 4 ) , luminal B breast cancer ( 4 ) , breast cancer, surrounding tissue ( 4 ) , breast cancer, triple negative ( 4 , 15 ) , endometrial cancer ( 1 ) , endometrial adenocarcinoma ( 1 ) , leukemia ( 42 , 54 ) , acute myelogenous leukemia ( 54 ) , chronic myelogenous leukemia ( 42 ) , hepatocellular carcinoma, surrounding tissue ( 32 ) , lung cancer ( 13 , 24 , 26 , 46 ) , non-small cell lung cancer ( 24 , 46 ) , non-small cell lung adenocarcinoma ( 13 , 26 ) , ovarian cancer ( 1 , 15 ) , pancreatic ductal adenocarcinoma ( 19 ) , multiple myeloma ( 3 ) , melanoma skin cancer ( 10 )
Relevant cell line - cell type - tissue:
'pancreatic, ductal'-pancreas ( 19 ) , 'stem, embryonic' ( 35 ) , 293 (epithelial) ( 12 , 36 ) , 293 (epithelial) [AT1 (human), transfection, AT1R stable transfected HEK293] ( 30 ) , 293 (epithelial) [AT1 (human), transfection] ( 29 ) , 293T (epithelial) ( 9 ) , 786-O (renal) ( 7 ) , 786-O (renal) [VHL (human), transfection] ( 7 ) , A431 (epithelial) ( 2 ) , A498 (renal) ( 31 ) , breast ( 4 , 15 ) , BT-474 (breast cell) ( 6 ) , H2009 (pulmonary) ( 24 ) , H2077 (pulmonary) ( 24 ) , H2887 (pulmonary) ( 24 ) , H322M (pulmonary) ( 24 ) , HEC-1B (endometrial) ( 1 ) , HeLa (cervical) ( 5 , 8 , 14 , 23 , 28 , 33 , 39 , 41 , 43 , 45 , 48 , 49 , 50 , 52 , 53 ) , hepatocyte-liver ( 32 ) , HMLER ('stem, breast cancer') ( 16 ) , HMLER ('stem, breast cancer') [CXCR4 (human), knockdown] ( 16 ) , HOS (bone cell) ( 46 ) , HTBoA (ovarian) ( 1 ) , HUES-9 ('stem, embryonic') ( 27 ) , Jurkat (T lymphocyte) ( 21 , 38 , 40 ) , K562 (erythroid) ( 23 , 42 , 51 ) , KMS-18 (B lymphocyte) ( 3 ) , liver ( 18 ) , MCAS (ovarian) ( 1 ) , MCF-7 (breast cell) ( 6 ) , MDA-MB-231 (breast cell) ( 2 ) , MEF (fibroblast) ( 8 ) , MM.1S (lymphoblast) ( 3 ) , myocyte-heart ( 12 ) , NCI-H1395 (pulmonary) ( 24 ) , NCI-H2030 (pulmonary) ( 24 ) , NCI-H358 (pulmonary) ( 46 ) , ovary ( 15 ) , PC9 (pulmonary) ( 13 ) , REG ( 34 ) , RPMI-8226 (plasma cell) ( 3 ) , THP1 (myeloid) ( 54 ) , U-1810 (pulmonary) ( 26 ) , U-1810 (pulmonary) [EFNB3 (human), knockdown] ( 26 ) , U266 (plasma cell) ( 3 ) , U2OS (bone cell) [GR (human)] ( 44 ) , WM115 (melanocyte) ( 37 ) , WM239A (epidermal) ( 10 )

Upstream Regulation
Kinases, in vitro:
ERK1 (human) ( 54 ) , P38A (human) ( 2 ) , P38B (human) ( 2 ) , P38D (human) ( 2 ) , P38G (human) ( 2 )
Treatments:
heat_shock ( 51 ) , SII_angiotensin_2 ( 29 ) , virus infection ( 5 )

Downstream Regulation
Effects of modification on HSF1:
activity, inhibited ( 54 ) , intracellular localization ( 46 , 50 ) , molecular association, regulation ( 50 ) , phosphorylation ( 11 ) , protein degradation ( 46 ) , sumoylation ( 52 )
Effects of modification on biological processes:
transcription, induced ( 53 ) , transcription, inhibited ( 8 , 50 , 54 )
Induce interaction with:
14-3-3 epsilon (human) ( 50 )

References 

1

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

2

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

3

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

4

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

5

Qiu Y, et al. (2016) Hsp70-1: upregulation via selective phosphorylation of heat shock factor 1 during coxsackieviral infection and promotion of viral replication via the AU-rich element. Cell Mol Life Sci 73, 1067-84
26361762   Curated Info

6

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

7

Malec V, Coulson JM, Urbé S, Clague MJ (2015) Combined Analyses of the VHL and Hypoxia Signaling Axes in an Isogenic Pairing of Renal Clear Cell Carcinoma Cells. J Proteome Res 14, 5263-72
26506913   Curated Info

8

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

9

Franchin C, et al. (2015) Quantitative analysis of a phosphoproteome readily altered by the protein kinase CK2 inhibitor quinalizarin in HEK-293T cells. Biochim Biophys Acta 1854, 609-23
25278378   Curated Info

10

Stuart SA, et al. (2015) A Phosphoproteomic Comparison of B-RAFV600E and MKK1/2 Inhibitors in Melanoma Cells. Mol Cell Proteomics 14, 1599-615
25850435   Curated Info

11

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

12

Meijering RA, et al. (2015) RhoA Activation Sensitizes Cells to Proteotoxic Stimuli by Abrogating the HSF1-Dependent Heat Shock Response. PLoS One 10, e0133553
26193369   Curated Info

13

Tsai CF, et al. (2015) Large-scale determination of absolute phosphorylation stoichiometries in human cells by motif-targeting quantitative proteomics. Nat Commun 6, 6622
25814448   Curated Info

14

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

15

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

16

Yi T, et al. (2014) Quantitative phosphoproteomic analysis reveals system-wide signaling pathways downstream of SDF-1/CXCR4 in breast cancer stem cells. Proc Natl Acad Sci U S A 111, E2182-90
24782546   Curated Info

17

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

18

Bian Y, et al. (2014) An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics 96, 253-62
24275569   Curated Info

19

Britton D, et al. (2014) Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets. PLoS One 9, e90948
24670416   Curated Info

20

Schweppe DK, Rigas JR, Gerber SA (2013) Quantitative phosphoproteomic profiling of human non-small cell lung cancer tumors. J Proteomics 91, 286-96
23911959   Curated Info

21

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

22

Shiromizu T, et al. (2013) Identification of missing proteins in the neXtProt database and unregistered phosphopeptides in the PhosphoSitePlus database as part of the Chromosome-centric Human Proteome Project. J Proteome Res 12, 2414-21
23312004   Curated Info

23

Zhou H, et al. (2013) Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res 12, 260-71
23186163   Curated Info

24

Klammer M, et al. (2012) Phosphosignature predicts dasatinib response in non-small cell lung cancer. Mol Cell Proteomics 11, 651-68
22617229   Curated Info

25

Beli P, et al. (2012) Proteomic Investigations Reveal a Role for RNA Processing Factor THRAP3 in the DNA Damage Response. Mol Cell 46, 212-25
22424773   Curated Info

26

Ståhl S, et al. (2011) Phosphoproteomic profiling of NSCLC cells reveals that ephrin B3 regulates pro-survival signaling through Akt1-mediated phosphorylation of the EphA2 receptor. J Proteome Res 10, 2566-78
21413766   Curated Info

27

Rigbolt KT, et al. (2011) System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal 4, rs3
21406692   Curated Info

28

Kettenbach AN, et al. (2011) Quantitative phosphoproteomics identifies substrates and functional modules of aurora and polo-like kinase activities in mitotic cells. Sci Signal 4, rs5
21712546   Curated Info

29

Xiao K, et al. (2010) Global phosphorylation analysis of beta-arrestin-mediated signaling downstream of a seven transmembrane receptor (7TMR). Proc Natl Acad Sci U S A 107, 15299-304
20686112   Curated Info

30

Christensen GL, et al. (2010) Quantitative phosphoproteomics dissection of seven-transmembrane receptor signaling using full and biased agonists. Mol Cell Proteomics 9, 1540-53
20363803   Curated Info

31

Schreiber TB, et al. (2010) An integrated phosphoproteomics work flow reveals extensive network regulation in early lysophosphatidic acid signaling. Mol Cell Proteomics 9, 1047-62
20071362   Curated Info

32

Han G, et al. (2010) Phosphoproteome analysis of human liver tissue by long-gradient nanoflow LC coupled with multiple stage MS analysis. Electrophoresis 31, 1080-9
20166139   Curated Info

33

Pan C, Olsen JV, Daub H, Mann M (2009) Global effects of kinase inhibitors on signaling networks revealed by quantitative phosphoproteomics. Mol Cell Proteomics 8, 2796-808
19651622   Curated Info

34

Brunet Simioni M, et al. (2009) Heat shock protein 27 is involved in SUMO-2/3 modification of heat shock factor 1 and thereby modulates the transcription factor activity. Oncogene 28, 3332-44
19597476   Curated Info

35

Brill LM, et al. (2009) Phosphoproteomic analysis of human embryonic stem cells. Cell Stem Cell 5, 204-13
19664994   Curated Info

36

Gauci S, et al. (2009) Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem 81, 4493-501
19413330   Curated Info

37

Old WM, et al. (2009) Functional proteomics identifies targets of phosphorylation by B-Raf signaling in melanoma. Mol Cell 34, 115-31
19362540   Curated Info

38

Possemato A (2009) CST Curation Set: 6371; Year: 2009; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pSP
Curated Info

39

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

40

Possemato A (2009) CST Curation Set: 6369; Year: 2009; Biosample/Treatment: cell line, Jurkat/calyculin_A & pervanadate; Disease: T cell leukemia; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: pSP
Curated Info

41

Dephoure N, et al. (2008) A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A 105, 10762-7
18669648   Curated Info

42

Stokes M (2008) CST Curation Set: 4394; 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

43

McNulty DE, Annan RS (2008) Hydrophilic interaction chromatography reduces the complexity of the phosphoproteome and improves global phosphopeptide isolation and detection. Mol Cell Proteomics 7, 971-80
18212344   Curated Info

44

Lowery DM, et al. (2007) Proteomic screen defines the Polo-box domain interactome and identifies Rock2 as a Plk1 substrate. EMBO J 26, 2262-73
17446864   Curated Info

45

Olsen JV, et al. (2006) Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127, 635-48
17081983   Curated Info

46

Seo HR, et al. (2006) Heat shock protein 25 or inducible heat shock protein 70 activates heat shock factor 1: dephosphorylation on serine 307 through inhibition of ERK1/2 phosphorylation. J Biol Chem 281, 17220-7
16624816   Curated Info

47

Hietakangas V, et al. (2006) PDSM, a motif for phosphorylation-dependent SUMO modification. Proc Natl Acad Sci U S A 103, 45-50
16371476   Curated Info

48

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
15760475   Curated Info

49

Beausoleil SA, et al. (2004) Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A 101, 12130-5
15302935   Curated Info

50

Wang X, Grammatikakis N, Siganou A, Calderwood SK (2003) 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 23, 6013-26
12917326   Curated Info

51

Hietakangas V, et al. (2003) Phosphorylation of serine 303 is a prerequisite for the stress-inducible SUMO modification of heat shock factor 1. Mol Cell Biol 23, 2953-68
12665592   Curated Info

52

Hilgarth RS, Hong Y, Park-Sarge OK, Sarge KD (2003) Insights into the regulation of heat shock transcription factor 1 SUMO-1 modification. Biochem Biophys Res Commun 303, 196-200
12646186   Curated Info

53

Xia W, et al. (1998) Transcriptional activation of heat shock factor HSF1 probed by phosphopeptide analysis of factor 32P-labeled in vivo. J Biol Chem 273, 8749-55
9535852   Curated Info

54

Chu B, et al. (1996) Sequential phosphorylation by mitogen-activated protein kinase and glycogen synthase kinase 3 represses transcriptional activation by heat shock factor-1. J Biol Chem 271, 30847-57
8940068   Curated Info