Ser315
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Home > Phosphorylation Site Page: > Ser315  -  p53 (human)

Site Information
LPNNtsssPQPkkkP   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447530

In vivo Characterization
Methods used to characterize site in vivo:
2D analysis ( 52 ) , [32P] bio-synthetic labeling ( 38 ) , back-titration ( 46 ) , immunoassay ( 3 ) , immunoprecipitation ( 1 , 3 , 44 ) , mass spectrometry ( 3 , 5 , 6 , 7 , 10 , 11 , 12 , 13 , 15 , 16 , 19 , 20 , 23 , 24 , 29 , 30 , 36 , 46 , 48 ) , mass spectrometry (in vitro) ( 1 ) , modification-specific antibody ( 40 ) , mutation of modification site ( 1 , 3 , 4 , 9 , 14 , 17 , 21 , 28 , 33 , 34 , 35 , 38 , 40 , 41 , 42 , 45 , 47 ) , phospho-antibody ( 1 , 3 , 17 , 18 , 21 , 22 , 26 , 27 , 32 , 34 , 35 , 37 , 39 , 40 , 41 , 43 , 44 , 47 ) , phosphopeptide mapping ( 52 ) , western blotting ( 1 , 3 , 17 , 18 , 21 , 26 , 27 , 32 , 40 , 47 , 52 )
Disease tissue studied:
ataxia-telangiectasia ( 44 ) , bone cancer ( 1 , 27 , 28 , 47 ) , brain cancer ( 52 ) , glioblastoma ( 52 ) , glioblastoma multiforme ( 52 ) , glioma ( 52 ) , breast cancer ( 3 , 6 , 10 , 47 ) , colorectal cancer ( 1 , 21 , 28 , 40 ) , colorectal carcinoma ( 1 , 21 , 28 , 40 ) , leukemia ( 11 , 48 ) , acute myelogenous leukemia ( 11 , 48 ) , acute erythroid leukemias, including erythroleukemia (M6a) and very rare pure erythroid leukemia (M6b) ( 11 ) , lung cancer ( 3 , 7 , 10 , 16 , 22 , 28 , 40 , 52 ) , non-small cell lung cancer ( 3 , 10 , 22 , 28 , 40 , 52 ) , non-small cell lung adenocarcinoma ( 7 , 52 ) , neuroblastoma ( 14 , 18 , 44 ) , melanoma skin cancer ( 47 )
Relevant cell line - cell type - tissue:
'stem, embryonic' ( 35 ) , 293 (epithelial) [AT1 (human), transfection, AT1R stable transfected HEK293] ( 20 ) , 293 (epithelial) [AT1 (human), transfection] ( 19 ) , 293 (epithelial) ( 1 , 4 , 9 , 24 , 39 ) , 293E (epithelial) ( 15 ) , 293FT ( 27 ) , 3T3 (fibroblast) [SHP-2 (mouse), homozygous knockout] ( 34 , 38 ) , A375 (melanocyte) ( 47 ) , A549 (pulmonary) ( 40 ) , AML-193 (monocyte) ( 11 ) , AT24RM (lymphoblastoid) ( 44 ) , BT (epithelial) ( 44 ) , BT-20 (breast cell) ( 10 ) , BT-549 (breast cell) ( 10 ) , C3ABR (lymphoblastoid) ( 44 ) , Calu 6 (pulmonary) ( 52 ) , CL1-0 (pulmonary) ( 16 ) , CL1-1 (pulmonary) ( 16 ) , CL1-2 (pulmonary) ( 16 ) , CL1-5 (pulmonary) ( 16 ) , COS (fibroblast) ( 32 ) , endothelial-aorta ( 12 ) , ESC ( 26 ) , fibroblast-skin ( 30 ) , Flp-In T-Rex-293 (epithelial) [PRKD1 (human), genetic knockin] ( 13 ) , Flp-In T-Rex-293 (epithelial) ( 13 ) , GM01526 (lymphoblast) ( 44 ) , GM02254 (lymphoblast) ( 44 ) , H2009 (pulmonary) ( 10 ) , H2077 (pulmonary) ( 10 ) , H2887 (pulmonary) ( 10 ) , H322M (pulmonary) ( 10 ) , HCC1359 (pulmonary) ( 10 ) , HCC1937 (breast cell) ( 10 ) , HCC2279 (pulmonary) ( 10 ) , HCC366 (pulmonary) ( 10 ) , HCC4006 (pulmonary) ( 10 ) , HCC78 (pulmonary) ( 10 ) , HCT116 (intestinal) [p53 (human), homozygous knockout] ( 21 ) , HCT116 (intestinal) ( 1 , 28 , 40 ) , HEK293T (epithelial) ( 29 ) , HEL (erythroid) ( 11 ) , HeLa (cervical) ( 5 , 17 , 36 , 38 ) , HMLER ('stem, breast cancer') [CXCR4 (human), knockdown] ( 6 ) , HMLER ('stem, breast cancer') ( 6 ) , HOP62 (pulmonary) ( 10 ) , HT1080 (fibroblast) ( 38 ) , HUES-7 ('stem, embryonic') ( 23 ) , IMR-90 (fibroblast) ( 43 ) , IMR32 (neural crest) ( 18 ) , L3 (lymphoblastoid) ( 44 ) , lung ( 7 ) , MCF-10A (breast cell) ( 3 ) , MCF-7 (breast cell) ( 10 , 39 , 47 ) , MDA-MB-231 (breast cell) ( 10 ) , MDA-MB-468 (breast cell) ( 10 ) , MEF (fibroblast) ( 4 , 40 ) , MEF (fibroblast) [IGF1R (mouse)] ( 33 , 45 ) , MRC5 (fibroblast) ( 40 ) , MV4-11 (macrophage) ( 11 ) , NCI-H1299 (pulmonary) ( 3 , 28 , 34 , 39 , 40 ) , NCI-H1395 (pulmonary) ( 10 ) , NCI-H157 (pulmonary) ( 10 ) , NCI-H1648 (pulmonary) ( 10 ) , NCI-H1666 (pulmonary) ( 10 ) , NCI-H2030 (pulmonary) ( 10 ) , NCI-H2172 (pulmonary) ( 10 ) , NCI-H322 (pulmonary) ( 10 ) , NCI-H460 (pulmonary) ( 22 ) , NCI-H520 (squamous) ( 10 ) , OCI/AML3 (myeloid) ( 48 ) , P31/FUJ (erythroid) ( 11 ) , PC9 (pulmonary) ( 10 ) , Saos-2 (bone cell) ( 1 , 28 , 42 , 47 ) , SF9 ( 37 , 46 , 47 ) , SH-SY5Y (neural crest) ( 14 ) , SHEP (neuron) ( 44 ) , SW480 (intestinal) ( 39 ) , T98G (glial) [p53 (human), transfection] ( 52 ) , U2OS (bone cell) [GR (human)] ( 41 ) , U2OS (bone cell) ( 27 ) , WI-38 (fibroblast) ( 38 ) , WS1 (fibroblast) ( 40 )

Upstream Regulation
Regulatory protein:
CCNB1 (human) ( 17 , 21 ) , DUSP26 (human) ( 18 ) , LATS1 (human) ( 3 ) , LATS2 (human) ( 3 )
Putative in vivo kinases:
AurA (human) ( 1 , 39 ) , CDK1 (human) ( 17 , 21 , 47 ) , NEK2 (human) ( 1 )
Kinases, in vitro:
AurA (human) ( 1 , 9 ) , CDK1 (human) ( 21 , 47 , 51 ) , CDK2 (human) ( 37 , 46 , 51 ) , CDK9 (human) ( 31 ) , NEK2 (human) ( 1 )
Putative upstream phosphatases:
CDC14A (human) ( 32 )
Phosphatases, in vitro:
CDC14A (human) ( 49 ) , CDC14B (human) ( 49 )
Treatments:
2-deoxyglucose ( 22 ) , adriamycin ( 40 , 44 ) , ionizing_radiation ( 21 , 40 , 44 ) , LLnL ( 41 ) , MBA ( 35 ) , metastatic potential ( 16 ) , nocodazole ( 17 , 40 ) , nutlin-3 ( 26 ) , okadaic_acid ( 46 ) , PALA ( 40 ) , R03306 ( 17 ) , retinoic_acid ( 35 ) , seliciclib ( 47 ) , siRNA ( 1 ) , taxol ( 40 ) , thapsigargin ( 38 ) , thymidine ( 17 ) , tunicamycin ( 38 ) , UV ( 35 , 40 , 41 , 43 , 47 ) , ZM447439 ( 17 )

Downstream Regulation
Effects of modification on p53:
activity, induced ( 35 ) , activity, inhibited ( 39 ) , intracellular localization ( 33 , 34 , 38 ) , molecular association, regulation ( 3 , 28 , 34 , 41 , 42 , 51 ) , protein conformation ( 51 ) , protein degradation ( 1 , 17 , 33 , 39 ) , ubiquitination ( 4 )
Effects of modification on biological processes:
apoptosis, altered ( 17 , 21 ) , apoptosis, induced ( 28 ) , apoptosis, inhibited ( 1 , 38 , 39 ) , cell cycle regulation ( 1 , 39 , 45 ) , cell growth, altered ( 35 ) , cell motility, altered ( 4 ) , cell motility, inhibited ( 3 ) , transcription, altered ( 35 , 42 ) , transcription, induced ( 28 , 47 ) , transcription, inhibited ( 1 )
Induce interaction with:
DNA ( 28 , 51 ) , PIN1 (human) ( 28 , 41 , 42 )
Inhibit interaction with:
NFkB-p100 (human) ( 3 )

References 

1

Choi BK, et al. (2018) Literature-based automated discovery of tumor suppressor p53 phosphorylation and inhibition by NEK2. Proc Natl Acad Sci U S A 115, 10666-10671
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2

Boeing S, et al. (2016) Multiomic Analysis of the UV-Induced DNA Damage Response. Cell Rep 15, 1597-1610
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3

Furth N, et al. (2015) Down-regulation of LATS kinases alters p53 to promote cell migration. Genes Dev 29, 2325-30
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4

Jha HC, et al. (2015) EBNA3C regulates p53 through induction of Aurora kinase B. Oncotarget 6, 5788-803
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5

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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6

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
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7

Schweppe DK, Rigas JR, Gerber SA (2013) Quantitative phosphoproteomic profiling of human non-small cell lung cancer tumors. J Proteomics 91, 286-96
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8

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
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9

Hsueh KW, et al. (2013) A novel Aurora-A-mediated phosphorylation of p53 inhibits its interaction with MDM2. Biochim Biophys Acta 1834, 508-515
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10

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

Alcolea MP, et al. (2012) Phosphoproteomic analysis of leukemia cells under basal and drug-treated conditions identifies markers of kinase pathway activation and mechanisms of resistance. Mol Cell Proteomics 11, 453-66
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12

Verano-Braga T, et al. (2012) Time-resolved quantitative phosphoproteomics: new insights into Angiotensin-(1-7) signaling networks in human endothelial cells. J Proteome Res 11, 3370-81
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13

Franz-Wachtel M, et al. (2012) Global detection of protein kinase D-dependent phosphorylation events in nocodazole-treated human cells. Mol Cell Proteomics 11, 160-70
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14

Grison A, et al. (2011) Ser46 phosphorylation and prolyl-isomerase Pin1-mediated isomerization of p53 are key events in p53-dependent apoptosis induced by mutant huntingtin. Proc Natl Acad Sci U S A 108, 17979-84
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15

Hsu PP, et al. (2011) The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332, 1317-22
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16

Wang YT, et al. (2010) An informatics-assisted label-free quantitation strategy that depicts phosphoproteomic profiles in lung cancer cell invasion. J Proteome Res 9, 5582-97
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17

Kreis NN, et al. (2010) Restoration of the tumor suppressor p53 by downregulating cyclin B1 in human papillomavirus 16/18-infected cancer cells. Oncogene 29, 5591-603
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18

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
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19

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
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20

Christensen GL, et al. (2010) Quantitative phosphoproteomics dissection of seven-transmembrane receptor signaling using full and biased agonists. Mol Cell Proteomics 9, 1540-53
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21

Nantajit D, et al. (2010) Cyclin B1/Cdk1 phosphorylation of mitochondrial p53 induces anti-apoptotic response. PLoS One 5, e12341
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22

Zhong D, et al. (2009) The Glycolytic Inhibitor 2-Deoxyglucose Activates Multiple Prosurvival Pathways through IGF1R. J Biol Chem 284, 23225-33
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23

Van Hoof D, et al. (2009) Phosphorylation dynamics during early differentiation of human embryonic stem cells. Cell Stem Cell 5, 214-26
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24

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
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25

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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26

Maimets T, Neganova I, Armstrong L, Lako M (2008) Activation of p53 by nutlin leads to rapid differentiation of human embryonic stem cells. Oncogene 27, 5277-87
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27

Chang PC, Li M (2008) Kaposi's sarcoma-associated herpesvirus K-cyclin interacts with Cdk9 and stimulates Cdk9-mediated phosphorylation of p53 tumor suppressor. J Virol 82, 278-90
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28

Mantovani F, et al. (2007) The prolyl isomerase Pin1 orchestrates p53 acetylation and dissociation from the apoptosis inhibitor iASPP. Nat Struct Mol Biol 14, 912-20
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29

Molina H, et al. (2007) Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry. Proc Natl Acad Sci U S A 104, 2199-204
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30

Yang F, et al. (2006) Phosphoproteome profiling of human skin fibroblast cells in response to low- and high-dose irradiation. J Proteome Res 5, 1252-60
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31

Radhakrishnan SK, Gartel AL (2006) CDK9 phosphorylates p53 on serine residues 33, 315 and 392. Cell Cycle 5, 519-21
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32

Paulsen MT, et al. (2006) The p53-targeting human phosphatase hCdc14A interacts with the Cdk1/cyclin B complex and is differentially expressed in human cancers. Mol Cancer 5, 25
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33

Pluquet O, Qu LK, Baltzis D, Koromilas AE (2005) Endoplasmic reticulum stress accelerates p53 degradation by the cooperative actions of Hdm2 and glycogen synthase kinase 3beta. Mol Cell Biol 25, 9392-405
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34

Fogal V, et al. (2005) Cell cycle-dependent nuclear retention of p53 by E2F1 requires phosphorylation of p53 at Ser315. EMBO J 24, 2768-82
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35

Lin T, et al. (2005) p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Nat Cell Biol 7, 165-71
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36

Beausoleil SA, et al. (2004) Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A 101, 12130-5
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37

Pospísilová S, et al. (2004) Activation of the DNA-binding ability of latent p53 protein by protein kinase C is abolished by protein kinase CK2. Biochem J 378, 939-47
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38

Qu L, et al. (2004) Endoplasmic reticulum stress induces p53 cytoplasmic localization and prevents p53-dependent apoptosis by a pathway involving glycogen synthase kinase-3beta. Genes Dev 18, 261-77
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39

Katayama H, et al. (2004) Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet 36, 55-62
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40

Saito S, et al. (2003) Phosphorylation site interdependence of human p53 post-translational modifications in response to stress. J Biol Chem 278, 37536-44
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41

Zheng H, et al. (2002) The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response. Nature 419, 849-53
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42

Zacchi P, et al. (2002) The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults. Nature 419, 853-7
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43

Bulavin DV, et al. (2002) Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity. Nat Genet 31, 210-5
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44

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
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45

Tarapore P, Tokuyama Y, Horn HF, Fukasawa K (2001) Difference in the centrosome duplication regulatory activity among p53 'hot spot' mutants: potential role of Ser 315 phosphorylation-dependent centrosome binding of p53. Oncogene 20, 6851-63
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46

Merrick BA, et al. (2001) Site-specific phosphorylation of human p53 protein determined by mass spectrometry. Biochemistry 40, 4053-66
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47

Blaydes JP, et al. (2001) Stoichiometric phosphorylation of human p53 at Ser315 stimulates p53-dependent transcription. J Biol Chem 276, 4699-708
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48

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
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49

Li L, Ljungman M, Dixon JE (2000) The human Cdc14 phosphatases interact with and dephosphorylate the tumor suppressor protein p53. J Biol Chem 275, 2410-4
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50

Sakaguchi K, et al. (1997) Phosphorylation of serine 392 stabilizes the tetramer formation of tumor suppressor protein p53. Biochemistry 36, 10117-24
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51

Wang Y, Prives C (1995) Increased and altered DNA binding of human p53 by S and G2/M but not G1 cyclin-dependent kinases. Nature 376, 88-91
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52

Ullrich SJ, et al. (1993) Phosphorylation at Ser-15 and Ser-392 in mutant p53 molecules from human tumors is altered compared to wild-type p53. Proc Natl Acad Sci U S A 90, 5954-8
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53

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
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