Ser37
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Home > Phosphorylation Site Page: > Ser37  -  p53 (human)

Site Information
NVLsPLPsQAMDDLM   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447532

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 34 ) , [32P] bio-synthetic labeling ( 54 ) , flow cytometry ( 18 ) , immunoprecipitation ( 6 , 11 , 45 ) , mass spectrometry ( 52 , 58 ) , modification-specific antibody ( 38 , 56 ) , mutation of modification site ( 6 , 19 , 21 , 26 , 27 , 31 , 35 , 36 , 38 , 44 , 48 , 50 , 53 , 54 , 55 ) , phospho-antibody ( 6 , 8 , 10 , 11 , 12 , 16 , 18 , 19 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 34 , 36 , 37 , 38 , 40 , 41 , 42 , 43 , 45 , 46 , 47 , 49 , 51 , 56 , 61 ) , phosphoamino acid analysis ( 21 ) , western blotting ( 6 , 8 , 10 , 11 , 12 , 16 , 18 , 19 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 29 , 31 , 34 , 36 , 38 , 40 , 42 , 51 , 56 )
Disease tissue studied:
ataxia-telangiectasia ( 29 , 45 ) , bone cancer ( 6 , 21 , 25 , 34 ) , brain cancer ( 31 ) , glioblastoma ( 31 ) , glioma ( 31 ) , breast cancer ( 36 ) , colorectal cancer ( 19 , 25 , 35 , 38 ) , colorectal carcinoma ( 19 , 25 , 35 , 38 ) , leukemia ( 12 , 23 , 36 , 55 , 58 ) , acute lymphocytic leukemia ( 12 ) , acute myelogenous leukemia ( 23 , 58 ) , T cell leukemia ( 36 , 55 ) , liver cancer ( 8 ) , hepatocellular carcinoma ( 8 ) , lung cancer ( 6 , 21 , 37 , 38 , 42 , 43 ) , non-small cell lung cancer ( 6 , 21 , 38 ) , non-small cell lung adenocarcinoma ( 6 ) , neuroblastoma ( 11 , 45 ) , prostate cancer ( 23 , 27 ) , melanoma skin cancer ( 22 )
Relevant cell line - cell type - tissue:
293 (epithelial) ( 11 ) , A2182 ( 51 ) , A549 (pulmonary) ( 6 , 37 , 38 , 42 , 43 ) , Aspc1 (pancreatic) ( 51 ) , AT1ABR (lymphoblastoid) ( 29 ) , AT24RM (lymphoblastoid) ( 45 ) , AT2KY ( 47 ) , AT5BI (fibroblast) ( 47 ) , AT5BIVA (fibroblast) ( 50 ) , BJ (fibroblast) ( 24 ) , BT (epithelial) ( 29 , 45 ) , C3ABR (lymphoblastoid) ( 29 , 45 ) , CCRF-CEM (T lymphocyte) ( 55 ) , chondrocyte ( 44 ) , COLO-320 (intestinal) ( 51 ) , COS (fibroblast) ( 48 ) , E.coli (bacterial) ( 9 ) , GM01526 (lymphoblast) ( 45 ) , GM02254 (lymphoblast) ( 45 ) , GM638 (fibroblast) ( 47 ) , HCC (hepatic) ( 8 ) , HCT116 (intestinal) ( 19 , 30 , 35 , 38 ) , HE49 (embryonic) ( 47 ) , HEK293T (epithelial) ( 46 ) , hepatocyte-liver ( 8 ) , HepG2 (hepatic) ( 8 ) , HSF (fibroblast) ( 26 ) , HT116 ( 51 ) , HUVEC (endothelial) ( 16 ) , IMR32 (neural crest) ( 11 ) , L3 (lymphoblastoid) ( 45 ) , leukocyte-blood ( 23 ) , LNCaP (prostate cell) ( 23 ) , M059J (glial) ( 31 ) , MCF-7 (breast cell) ( 36 , 41 , 61 ) , MDAH041 (fibroblast) ( 53 ) , MEF (fibroblast) ( 38 ) , MOLM 13 (myeloid) ( 23 ) , MOLT-4 (T lymphocyte) ( 36 ) , MRC5 (fibroblast) ( 38 ) , MT1 (lymphoblastoid) ( 32 ) , NALM6 (B lymphocyte) ( 12 ) , NCI-H1299 (pulmonary) ( 6 , 21 , 38 , 48 , 54 , 61 ) , NCI-H596 (pulmonary) ( 51 ) , NHF (fibroblast) ( 40 , 56 ) , OCI/AML3 (myeloid) ( 58 ) , OM431 ( 51 ) , PC3 (prostate cell) ( 27 ) , RKO (intestinal) ( 30 , 46 ) , SF9 ( 52 ) , SHEP (neuron) ( 45 ) , SJSA-1 (bone cell) ( 51 ) , SW680 (intestinal) ( 51 ) , T1 ( 22 ) , TK6 (lymphoblastoid) ( 32 ) , U2OS (bone cell) [GR (human)] ( 28 ) , U2OS (bone cell) ( 6 , 21 , 25 , 34 ) , WM4 ( 51 ) , WM5 ( 51 ) , WM793 ( 51 ) , WS1 (fibroblast) ( 38 , 49 )

Upstream Regulation
Regulatory protein:
ATM (human) ( 6 , 21 ) , ATR (human) ( 6 ) , DUSP26 (human) ( 11 ) , HRas (human) ( 24 ) , MAPKAPK5 (human) ( 24 ) , MKK3 (human) ( 24 ) , Myc (human) ( 40 ) , PPP1CA (human) ( 27 ) , PPP2R5C (human) ( 25 )
Putative in vivo kinases:
MAPKAPK5 (human) ( 24 )
Kinases, in vitro:
ATR (human) ( 62 ) , Chk1 (human) ( 39 , 57 ) , Chk2 (human) ( 57 ) , CK1A (human) ( 3 ) , DNAPK (human) ( 27 , 31 , 33 , 39 , 59 , 60 , 64 , 65 ) , MAPKAPK5 (human) ( 9 , 24 )
Putative upstream phosphatases:
DUSP26 (human) ( 11 ) , PPP1CA (human) ( 27 )
Phosphatases, in vitro:
DUSP26 (human) ( 11 ) , PPP1CA (human) ( 27 ) , PPP2CA (human) ( 36 )
Treatments:
15d-PGJ2 ( 16 ) , adriamycin ( 11 , 12 , 18 , 29 , 30 , 34 , 38 , 45 , 54 ) , asbestos ( 42 ) , caffeine ( 37 ) , calyculin_A ( 27 ) , colforsin ( 12 ) , depsipeptide ( 7 ) , desferoxamine ( 46 ) , dexamethasone ( 43 ) , etoposide ( 30 , 63 ) , Go_6976 ( 8 ) , granzyme_B ( 22 ) , H2O2 ( 37 ) , heat_shock ( 47 ) , hydroxyurea ( 46 ) , hyperoxia ( 37 ) , hypoxia ( 46 ) , IBMX ( 12 ) , idarubicin ( 23 ) , ionizing_radiation ( 21 , 23 , 36 , 38 , 45 , 47 , 54 , 58 ) , MI-63 ( 18 ) , nocodazole ( 38 ) , nutlin-3 ( 18 ) , okadaic_acid ( 25 , 27 , 36 , 52 ) , PALA ( 38 ) , PGE2 ( 26 ) , pifithrin-alpha ( 22 ) , SB203580 ( 16 ) , siRNA ( 24 , 27 ) , SP600125 ( 16 ) , taxol ( 38 , 54 ) , TMZ ( 32 ) , UV ( 24 , 27 , 37 , 38 , 49 , 51 , 56 , 61 ) , virus infection ( 8 )

Downstream Regulation
Effects of modification on p53:
acetylation ( 19 ) , activity, induced ( 30 ) , molecular association, regulation ( 6 , 9 , 36 , 53 , 59 , 64 ) , phosphorylation ( 19 ) , protein conformation ( 64 ) , protein stabilization ( 9 , 53 )
Effects of modification on biological processes:
apoptosis, altered ( 30 ) , apoptosis, induced ( 27 , 35 , 55 ) , DNA repair, induced ( 6 ) , transcription, altered ( 35 , 64 ) , transcription, induced ( 27 , 53 , 55 ) , transcription, inhibited ( 36 )
Induce interaction with:
CBP (human) ( 9 ) , MDM2 (human) ( 53 ) , PPP2CA (human) ( 36 ) , RPA1 (human) ( 6 )
Inhibit interaction with:
MDM2 (human) ( 59 , 64 )

Disease / Diagnostics Relevance
Relevant diseases:
T cell leukemia ( 55 )

References 

1

Qin Z, et al. (2016) PCNA-Ub polyubiquitination inhibits cell proliferation and induces cell-cycle checkpoints. Cell Cycle 15, 3390-3401
27753536   Curated Info

2

Agarwal S, Bell CM, Rothbart SB, Moran RG (2015) AMP-activated Protein Kinase (AMPK) Control of mTORC1 Is p53- and TSC2-independent in Pemetrexed-treated Carcinoma Cells. J Biol Chem 290, 27473-86
26391395   Curated Info

3

Okuda M, Nishimura Y (2015) Real-time and simultaneous monitoring of the phosphorylation and enhanced interaction of p53 and XPC acidic domains with the TFIIH p62 subunit. Oncogenesis 4, e150
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4

Rao F, et al. (2014) Inositol pyrophosphates mediate the DNA-PK/ATM-p53 cell death pathway by regulating CK2 phosphorylation of Tti1/Tel2. Mol Cell 54, 119-32
24657168   Curated Info

5

Choi DW, et al. (2013) WIP1, a homeostatic regulator of the DNA damage response, is targeted by HIPK2 for phosphorylation and degradation. Mol Cell 51, 374-85
23871434   Curated Info

6

Serrano MA, et al. (2013) DNA-PK, ATM and ATR collaboratively regulate p53-RPA interaction to facilitate homologous recombination DNA repair. Oncogene 32, 2452-62
22797063   Curated Info

7

Wang H, et al. (2012) The HDAC inhibitor depsipeptide transactivates the p53/p21 pathway by inducing DNA damage. DNA Repair (Amst) 11, 146-56
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8

Knoll S, et al. (2011) Dissection of cell context-dependent interactions between HBx and p53 family members in regulation of apoptosis: a role for HBV-induced HCC. Cell Cycle 10, 3554-65
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9

Lee CW, et al. (2010) Graded enhancement of p53 binding to CREB-binding protein (CBP) by multisite phosphorylation. Proc Natl Acad Sci U S A 107, 19290-5
20962272   Curated Info

10

Park J, et al. (2010) Dyrk1A phosphorylates p53 and inhibits proliferation of embryonic neuronal cells. J Biol Chem 285, 31895-906
20696760   Curated Info

11

Shang X, et al. (2010) Dual-specificity phosphatase 26 is a novel p53 phosphatase and inhibits p53 tumor suppressor functions in human neuroblastoma. Oncogene 29, 4938-46
20562916   Curated Info

12

Safa M, et al. (2010) Inhibitory role of cAMP on doxorubicin-induced apoptosis in pre-B ALL cells through dephosphorylation of p53 serine residues. Apoptosis 15, 196-203
19882354   Curated Info

13

Nishimura T, et al. (2009) Hepatitis C virus impairs p53 via persistent overexpression of 3beta-hydroxysterol Delta24-reductase. J Biol Chem 284, 36442-52
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14

van Dieck J, et al. (2009) Posttranslational modifications affect the interaction of S100 proteins with tumor suppressor p53. J Mol Biol 394, 922-30
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15

Yadavilli S, Chen Z, Albrecht T, Muganda PM (2009) Mechanism of diepoxybutane-induced p53 regulation in human cells. J Biochem Mol Toxicol 23, 373-86
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16

Ho TC, et al. (2008) 15-deoxy-Delta(12,14)-prostaglandin J2 induces vascular endothelial cell apoptosis through the sequential activation of MAPKS and p53. J Biol Chem 283, 30273-88
18718914   Curated Info

17

Warnock LJ, et al. (2008) Influence of tetramerisation on site-specific post-translational modifications of p53: comparison of human and murine p53 tumor suppressor protein. Cancer Biol Ther 7, 1481-9
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18

Jones RJ, et al. (2008) Inhibition of the p53 E3 ligase HDM-2 induces apoptosis and DNA damage--independent p53 phosphorylation in mantle cell lymphoma. Clin Cancer Res 14, 5416-25
18765533   Curated Info

19

Warnock LJ, Adamson R, Lynch CJ, Milner J (2008) Crosstalk between site-specific modifications on p53 and histone H3. Oncogene 27, 1639-44
17891183   Curated Info

20

Wang H, et al. (2008) An ATM- and Rad3-related (ATR) Signaling Pathway and a Phosphorylation-Acetylation Cascade Are Involved in Activation of p53/p21Waf1/Cip1 in Response to 5-Aza-2'-deoxycytidine Treatment. J Biol Chem 283, 2564-74
17977830   Curated Info

21

Shouse GP, Cai X, Liu X (2008) Serine 15 phosphorylation of p53 directs its interaction with B56gamma and the tumor suppressor activity of B56gamma-specific protein phosphatase 2A. Mol Cell Biol 28, 448-56
17967874   Curated Info

22

Meslin F, et al. (2007) Granzyme B-induced cell death involves induction of p53 tumor suppressor gene and its activation in tumor target cells. J Biol Chem 282, 32991-9
17855337   Curated Info

23

Irish JM, et al. (2007) Flt3 Y591 duplication and Bcl-2 overexpression are detected in acute myeloid leukemia cells with high levels of phosphorylated wild-type p53. Blood 109, 2589-96
17105820   Curated Info

24

Sun P, et al. (2007) PRAK is essential for ras-induced senescence and tumor suppression. Cell 128, 295-308
17254968   Curated Info

25

Li HH, et al. (2007) A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55. EMBO J 26, 402-11
17245430   Curated Info

26

Faour WH, et al. (2006) Prostaglandin E2 stimulates p53 transactivational activity through specific serine 15 phosphorylation in human synovial fibroblasts. Role in suppression of c/EBP/NF-kappaB-mediated MEKK1-induced MMP-1 expression. J Biol Chem 281, 19849-60
16714289   Curated Info

27

Li DW, et al. (2006) Protein serine/threonine phosphatase-1 dephosphorylates p53 at Ser-15 and Ser-37 to modulate its transcriptional and apoptotic activities. Oncogene 25, 3006-22
16501611   Curated Info

28

Mayo LD, et al. (2005) Phosphorylation of human p53 at serine 46 determines promoter selection and whether apoptosis is attenuated or amplified. J Biol Chem 280, 25953-9
15843377   Curated Info

29

Kurz EU, Douglas P, Lees-Miller SP (2004) Doxorubicin activates ATM-dependent phosphorylation of multiple downstream targets in part through the generation of reactive oxygen species. J Biol Chem 279, 53272-81
15489221   Curated Info

30

Thompson T, et al. (2004) Phosphorylation of p53 on key serines is dispensable for transcriptional activation and apoptosis. J Biol Chem 279, 53015-22
15471885   Curated Info

31

Komiyama S, et al. (2004) Potentiality of DNA-dependent protein kinase to phosphorylate Ser46 of human p53. Biochem Biophys Res Commun 323, 816-22
15381073   Curated Info

32

Caporali S, et al. (2004) DNA damage induced by temozolomide signals to both ATM and ATR: role of the mismatch repair system. Mol Pharmacol 66, 478-91
15322239   Curated Info

33

Soubeyrand S, Schild-Poulter C, Haché RJ (2004) Structured DNA promotes phosphorylation of p53 by DNA-dependent protein kinase at serine 9 and threonine 18. Eur J Biochem 271, 3776-84
15355354   Curated Info

34

Jackson MW, et al. (2004) Limited role of N-terminal phosphoserine residues in the activation of transcription by p53. Oncogene 23, 4477-87
15064747   Curated Info

35

Kaeser MD, Pebernard S, Iggo RD (2004) Regulation of p53 stability and function in HCT116 colon cancer cells. J Biol Chem 279, 7598-605
14665630   Curated Info

36

Dohoney KM, et al. (2004) Phosphorylation of p53 at serine 37 is important for transcriptional activity and regulation in response to DNA damage. Oncogene 23, 49-57
14712210   Curated Info

37

Das KC, Dashnamoorthy R (2004) Hyperoxia activates the ATR-Chk1 pathway and phosphorylates p53 at multiple sites. Am J Physiol Lung Cell Mol Physiol 286, L87-97
12959929   Curated Info

38

Saito S, et al. (2003) Phosphorylation site interdependence of human p53 post-translational modifications in response to stress. J Biol Chem 278, 37536-44
12860987   Curated Info

39

Goudelock DM, et al. (2003) Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex. J Biol Chem 278, 29940-7
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40

Lindström MS, Wiman KG (2003) Myc and E2F1 induce p53 through p14ARF-independent mechanisms in human fibroblasts. Oncogene 22, 4993-5005
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41

Pluquet O, et al. (2003) The cytoprotective aminothiol WR1065 activates p53 through a non-genotoxic signaling pathway involving c-Jun N-terminal kinase. J Biol Chem 278, 11879-87
12531896   Curated Info

42

Matsuoka M, Igisu H, Morimoto Y (2003) Phosphorylation of p53 protein in A549 human pulmonary epithelial cells exposed to asbestos fibers. Environ Health Perspect 111, 509-12
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43

Urban G, et al. (2003) Identification of a functional link for the p53 tumor suppressor protein in dexamethasone-induced growth suppression. J Biol Chem 278, 9747-53
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44

Kim SJ, et al. (2002) p38 kinase regulates nitric oxide-induced apoptosis of articular chondrocytes by accumulating p53 via NFkappa B-dependent transcription and stabilization by serine 15 phosphorylation. J Biol Chem 277, 33501-8
12091386   Curated Info

45

Saito S, et al. (2002) ATM mediates phosphorylation at multiple p53 sites, including Ser(46), in response to ionizing radiation. J Biol Chem 277, 12491-4
11875057   Curated Info

46

Hammond EM, et al. (2002) Hypoxia links ATR and p53 through replication arrest. Mol Cell Biol 22, 1834-43
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47

Miyakoda M, Suzuki K, Kodama S, Watanabe M (2002) Activation of ATM and phosphorylation of p53 by heat shock. Oncogene 21, 1090-6
11850826   Curated Info

48

Dumaz N, Milne DM, Jardine LJ, Meek DW (2001) Critical roles for the serine 20, but not the serine 15, phosphorylation site and for the polyproline domain in regulating p53 turnover. Biochem J 359, 459-64
11583595   Curated Info

49

Latonen L, Taya Y, Laiho M (2001) UV-radiation induces dose-dependent regulation of p53 response and modulates p53-HDM2 interaction in human fibroblasts. Oncogene 20, 6784-93
11709713   Curated Info

50

Turenne GA, Paul P, Laflair L, Price BD (2001) Activation of p53 transcriptional activity requires ATM's kinase domain and multiple N-terminal serine residues of p53. Oncogene 20, 5100-10
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51

Minamoto T, et al. (2001) Distinct pattern of p53 phosphorylation in human tumors. Oncogene 20, 3341-7
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52

Merrick BA, et al. (2001) Site-specific phosphorylation of human p53 protein determined by mass spectrometry. Biochemistry 40, 4053-66
11300786   Curated Info

53

Bean LJ, Stark GR (2001) Phosphorylation of serines 15 and 37 is necessary for efficient accumulation of p53 following irradiation with UV. Oncogene 20, 1076-84
11314044   Curated Info

54

Stewart ZA, Tang LJ, Pietenpol JA (2001) Increased p53 phosphorylation after microtubule disruption is mediated in a microtubule inhibitor- and cell-specific manner. Oncogene 20, 113-24
11244509   Curated Info

55

Cinti C, et al. (2000) A serine 37 mutation associated with two missense mutations at highly conserved regions of p53 affect pro-apoptotic genes expression in a T-lymphoblastoid drug resistant cell line. Oncogene 19, 5098-105
11042698   Curated Info

56

Buschmann T, et al. (2000) p53 phosphorylation and association with murine double minute 2, c-Jun NH2-terminal kinase, p14ARF, and p300/CBP during the cell cycle and after exposure to ultraviolet irradiation. Cancer Res 60, 896-900
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57

Shieh SY, et al. (2000) The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev 14, 289-300
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58

Abraham J, Kelly J, Thibault P, Benchimol S (2000) Post-translational modification of p53 protein in response to ionizing radiation analyzed by mass spectrometry. J Mol Biol 295, 853-64
10656795   Curated Info

59

Kapoor M, et al. (2000) Cooperative phosphorylation at multiple sites is required to activate p53 in response to UV radiation. Oncogene 19, 358-64
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60

Dumaz N, Milne DM, Meek DW (1999) Protein kinase CK1 is a p53-threonine 18 kinase which requires prior phosphorylation of serine 15. FEBS Lett 463, 312-6
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61

Bulavin DV, et al. (1999) Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation. EMBO J 18, 6845-54
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62

Tibbetts RS, et al. (1999) A role for ATR in the DNA damage-induced phosphorylation of p53. Genes Dev 13, 152-7
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63

Sakaguchi K, et al. (1998) DNA damage activates p53 through a phosphorylation-acetylation cascade. Genes Dev 12, 2831-41
9744860   Curated Info

64

Shieh SY, Ikeda M, Taya Y, Prives C (1997) DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 91, 325-34
9363941   Curated Info

65

Lees-Miller SP, et al. (1992) Human DNA-activated protein kinase phosphorylates serines 15 and 37 in the amino-terminal transactivation domain of human p53. Mol Cell Biol 12, 5041-9
1406679   Curated Info