Ser37

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 ( 20 , 38 , 56 ) , mutation of modification site ( 6 , 7 , 19 , 21 , 26 , 27 , 31 , 35 , 36 , 38 , 44 , 48 , 50 , 53 , 54 , 55 ) , phospho-antibody ( 6 , 7 , 8 , 10 , 11 , 12 , 16 , 18 , 19 , 20 , 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 , 63 ) , phosphoamino acid analysis ( 21 ) , western blotting ( 6 , 7 , 8 , 10 , 11 , 12 , 16 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 29 , 31 , 34 , 36 , 38 , 40 , 42 , 51 , 56 , 63 )
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 ( 7 , 19 , 25 , 35 , 38 , 63 ) , colorectal carcinoma ( 7 , 19 , 25 , 35 , 38 , 63 ) , 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 , 7 , 20 , 21 , 37 , 38 , 42 , 43 , 63 ) , non-small cell lung cancer ( 6 , 7 , 20 , 21 , 38 , 63 ) , non-small cell lung adenocarcinoma ( 6 , 7 , 20 , 63 ) , 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 , 7 , 20 , 37 , 38 , 42 , 43 , 63 ) , 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) ( 7 , 19 , 30 , 35 , 38 , 63 ) , 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 , 7 , 20 , 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) ( 4 ) , 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 ) , 5-aza-CdR ( 20 ) , 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 ) , 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 , 63 ) , MI-63 ( 18 ) , NaB ( 7 ) , 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 ) , trichostatin_A ( 7 ) , UV ( 24 , 27 , 37 , 38 , 49 , 51 , 56 , 61 ) , UVC ( 63 ) , virus infection ( 8 )

Downstream Regulation
Effects of modification on p53:	acetylation ( 19 , 63 ) , 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	Cui D, et al. (2020) FBXW7 Confers Radiation Survival by Targeting p53 for Degradation. Cell Rep 31940492 Curated Info
2	Qin Z, et al. (2016) PCNA-Ub polyubiquitination inhibits cell proliferation and induces cell-cycle checkpoints. Cell Cycle 15, 3390-3401 27753536 Curated Info
3	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
4	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 26029824 Curated Info
5	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
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 22112863 Curated Info
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 22030623 Curated Info
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 19861417 Curated Info
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 19819244 Curated Info
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 20024960 Curated Info
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 18769132 Curated Info
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 12756247 Curated Info
40	Lindström MS, Wiman KG (2003) Myc and E2F1 induce p53 through p14ARF-independent mechanisms in human fibroblasts. Oncogene 22, 4993-5005 12902982 Curated Info
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 12676607 Curated Info
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 12519780 Curated Info
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 11865061 Curated Info
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 11526498 Curated Info
51	Minamoto T, et al. (2001) Distinct pattern of p53 phosphorylation in human tumors. Oncogene 20, 3341-7 11423984 Curated Info
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 10706102 Curated Info
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 10673501 Curated Info
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 10656682 Curated Info
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 10606744 Curated Info
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 10581258 Curated Info
62	Tibbetts RS, et al. (1999) A role for ATR in the DNA damage-induced phosphorylation of p53. Genes Dev 13, 152-7 9925639 Curated Info
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