Ser33
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Home > Phosphorylation Site Page: > Ser33  -  p53 (human)

Site Information
LPENNVLsPLPsQAM   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447531

In vivo Characterization
Methods used to characterize site in vivo:
[32P] ATP in vitro ( 5 , 29 ) , immunoprecipitation ( 5 , 20 , 30 ) , mass spectrometry ( 26 , 28 ) , modification-specific antibody ( 15 ) , mutation of modification site ( 1 , 3 , 5 , 11 , 14 , 15 , 16 , 17 , 18 , 21 , 22 , 23 , 25 , 29 , 30 ) , phospho-antibody ( 2 , 5 , 6 , 8 , 9 , 10 , 12 , 15 , 16 , 19 , 20 , 22 , 24 , 27 , 29 , 30 , 32 ) , western blotting ( 2 , 5 , 6 , 8 , 9 , 10 , 12 , 15 , 27 , 30 )
Disease tissue studied:
ataxia-telangiectasia ( 20 ) , adrenal cancer ( 2 ) , bone cancer ( 10 , 11 ) , colorectal cancer ( 9 , 11 , 14 , 15 ) , colorectal carcinoma ( 9 , 11 , 14 , 15 ) , leukemia ( 28 ) , acute myelogenous leukemia ( 28 ) , lung cancer ( 11 , 15 , 27 ) , non-small cell lung cancer ( 11 , 15 , 27 ) , lymphoma ( 30 ) , anaplastic large cell lymphoma ( 30 ) , neuroblastoma ( 1 , 8 , 12 , 20 ) , fibrosarcoma of soft tissue ( 2 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
ASK1 (human) ( 2 ) , CDK5 (mouse) ( 12 ) , CDK5R1 (mouse) ( 12 ) , HRas (human) ( 5 ) , MKK6 (human) ( 22 ) , Myc (human) ( 2 ) , P38A (human) ( 5 ) , P38B (human) ( 5 ) , P38G (human) ( 5 ) , PPM1D (human) ( 27 ) , RACK1 (human) ( 2 ) , RPS3 (human) ( 2 )
Putative in vivo kinases:
CDK9 (human) ( 10 ) , P38A (human) ( 2 , 22 , 27 , 29 ) , P38G (human) ( 5 )
Kinases, in vitro:
CDK5 (human) ( 12 ) , CDK7 (human) ( 32 ) , CDK9 (human) ( 13 ) , P38A (human) ( 3 , 5 , 29 ) , P38G (human) ( 5 )
Treatments:
15d-PGJ2 ( 6 ) , adriamycin ( 15 , 20 ) , Cdk2_inhibitor_II ( 8 ) , etoposide ( 31 ) , H2O2 ( 8 ) , ionizing_radiation ( 15 , 20 , 22 , 28 , 30 , 32 ) , LLnL ( 16 ) , MG132 ( 12 ) , mitomycin_C ( 12 ) , nocodazole ( 15 ) , okadaic_acid ( 26 ) , osmotic_stress ( 22 ) , PALA ( 15 ) , SB202190 ( 2 ) , SB203580 ( 6 , 22 , 27 ) , seliciclib ( 12 ) , siRNA ( 12 ) , SNP ( 12 ) , SP600125 ( 6 ) , taxol ( 15 ) , UV ( 15 , 16 , 19 , 24 , 27 , 29 , 30 ) , virus infection ( 19 ) , wortmannin ( 12 )

Downstream Regulation
Effects of modification on p53:
activity, induced ( 22 ) , molecular association, regulation ( 3 , 11 , 16 , 17 ) , phosphorylation ( 15 ) , protein stabilization ( 2 , 3 )
Effects of modification on biological processes:
apoptosis, induced ( 11 , 14 , 29 ) , cell cycle regulation ( 2 ) , cell growth, altered ( 10 ) , transcription, altered ( 14 , 17 , 22 ) , transcription, induced ( 5 , 11 )
Induce interaction with:
CBP (human) ( 3 ) , DNA ( 11 ) , PIN1 (human) ( 11 , 16 , 17 )

References 

1

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
22011578   Curated Info

2

Kim HD, Kim TS, Kim J (2011) Aberrant ribosome biogenesis activates c-Myc and ASK1 pathways resulting in p53-dependent G1 arrest. Oncogene 30, 3317-27
21383696   Curated Info

3

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

4

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

5

Kwong J, et al. (2009) p38alpha and p38gamma mediate oncogenic ras-induced senescence through differential mechanisms. J Biol Chem 284, 11237-46
19251701   Curated Info

6

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

7

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

8

Lee JH, et al. (2008) Cooperative roles of c-Abl and Cdk5 in regulation of p53 in response to oxidative stress. J Biol Chem 283, 19826-35
18490454   Curated Info

9

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

10

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
17942552   Curated Info

11

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
17906639   Curated Info

12

Lee JH, Kim HS, Lee SJ, Kim KT (2007) Stabilization and activation of p53 induced by Cdk5 contributes to neuronal cell death. J Cell Sci 120, 2259-71
17591690   Curated Info

13

Radhakrishnan SK, Gartel AL (2006) CDK9 phosphorylates p53 on serine residues 33, 315 and 392. Cell Cycle 5, 519-21
16552184   Curated Info

14

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

15

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

16

Zheng H, et al. (2002) The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response. Nature 419, 849-53
12397361   Curated Info

17

Zacchi P, et al. (2002) The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults. Nature 419, 853-7
12397362   Curated Info

18

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

19

Bulavin DV, et al. (2002) Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity. Nat Genet 31, 210-5
12021785   Curated Info

20

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

21

Bean LJ, Stark GR (2002) Regulation of the accumulation and function of p53 by phosphorylation of two residues within the domain that binds to Mdm2. J Biol Chem 277, 1864-71
11707453   Curated Info

22

Kishi H, et al. (2001) Osmotic shock induces G1 arrest through p53 phosphorylation at Ser33 by activated p38MAPK without phosphorylation at Ser15 and Ser20. J Biol Chem 276, 39115-22
11495913   Curated Info

23

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

24

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

25

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

26

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

27

Takekawa M, et al. (2000) p53-inducible wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation. EMBO J 19, 6517-26
11101524   Curated Info

28

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

29

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

30

Shieh SY, Taya Y, Prives C (1999) DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel site, Ser20, requires tetramerization. EMBO J 18, 1815-23
10202145   Curated Info

31

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

32

Ko LJ, et al. (1997) p53 is phosphorylated by CDK7-cyclin H in a p36MAT1-dependent manner. Mol Cell Biol 17, 7220-9
9372954   Curated Info