Thr18
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Home > Phosphorylation Site Page: > Thr18  -  p53 (human)

Site Information
EPPLsQEtFsDLWkL   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 447541

In vivo Characterization
Methods used to characterize site in vivo:
[32P] bio-synthetic labeling ( 22 ) , immunoprecipitation ( 11 , 18 ) , modification-specific antibody ( 16 ) , mutation of modification site ( 14 , 16 , 17 , 20 , 21 , 22 , 24 ) , phospho-antibody ( 1 , 7 , 10 , 11 , 14 , 16 , 18 , 23 , 24 ) , western blotting ( 1 , 7 , 10 , 11 , 16 , 23 , 24 )
Disease tissue studied:
ataxia-telangiectasia ( 18 ) , colorectal cancer ( 10 , 16 ) , colorectal carcinoma ( 10 , 16 ) , leukemia ( 11 ) , acute myelogenous leukemia ( 11 ) , liver cancer ( 1 ) , hepatocellular carcinoma ( 1 ) , lung cancer ( 10 , 16 , 24 ) , non-small cell lung cancer ( 10 , 16 , 24 ) , non-small cell squamous cell lung carcinoma ( 10 ) , neuroblastoma ( 18 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
LKB1 (human) ( 10 ) , plakophilin 2 (human) ( 1 ) , TERT (human) ( 23 ) , VRK1 (human) ( 1 , 7 )
Putative in vivo kinases:
CK1A (human) ( 11 ) , VRK1 (human) ( 1 , 14 )
Kinases, in vitro:
AMPKA1 (human) ( 13 ) , Chk1 (human) ( 13 ) , Chk2 (human) ( 13 , 25 ) , CK1D (human) ( 24 , 26 ) , DAPK1 (human) ( 13 ) , DNAPK (human) ( 15 ) , VRK1 (human) ( 14 )
Treatments:
adriamycin ( 14 , 18 ) , As2O3 ( 11 ) , bleomycin ( 23 ) , depsipeptide ( 5 ) , development ( 23 ) , high_glucose ( 1 ) , IC261 ( 11 ) , ionizing_radiation ( 11 , 16 , 18 , 23 , 24 ) , leptomycin_B ( 7 ) , low_glucose ( 1 ) , nocodazole ( 16 ) , PALA ( 16 ) , serum_starvation ( 23 ) , siRNA ( 1 , 10 ) , taxol ( 16 , 22 ) , UV ( 7 , 16 , 23 )

Downstream Regulation
Effects of modification on p53:
acetylation ( 5 , 16 , 18 ) , molecular association, regulation ( 3 , 4 , 8 , 21 , 24 ) , protein conformation ( 3 , 4 ) , protein stabilization ( 8 , 14 )
Effects of modification on biological processes:
apoptosis, altered ( 10 ) , transcription, altered ( 21 )
Induce interaction with:
CBP (human) ( 3 , 8 ) , p300 (human) ( 21 )
Inhibit interaction with:
MDM2 (human) ( 4 , 24 )

References 

1

Yokobori K, Miyauchi Y, Williams JG, Negishi M (2020) Phosphorylation of vaccinia-related kinase 1 at threonine 386 transduces glucose stress signal in human liver cells. Biosci Rep 40
32266931   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

Ithuralde RE, Turjanski AG (2016) Phosphorylation Regulates the Bound Structure of an Intrinsically Disordered Protein: The p53-TAZ2 Case. PLoS One 11, e0144284
26742101   Curated Info

4

ElSawy KM, et al. (2015) A spatiotemporal characterization of the effect of p53 phosphorylation on its interaction with MDM2. Cell Cycle 14, 179-88
25584963   Curated Info

5

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

6

Verkhivker GM (2012) Simulating Molecular Mechanisms of the MDM2-Mediated Regulatory Interactions: A Conformational Selection Model of the MDM2 Lid Dynamics. PLoS One 7, e40897
22815859   Curated Info

7

Valbuena A, Castro-Obregón S, Lazo PA (2011) Downregulation of VRK1 by p53 in response to DNA damage is mediated by the autophagic pathway. PLoS One 6, e17320
21386980   Curated Info

8

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

9

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

10

Zhong D, et al. (2008) LKB1 is necessary for Akt-mediated phosphorylation of proapoptotic proteins. Cancer Res 68, 7270-7
18794113   Curated Info

11

Alsheich-Bartok O, et al. (2008) PML enhances the regulation of p53 by CK1 in response to DNA damage. Oncogene 27, 3653-61
18246126   Curated Info

12

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

13

Craig AL, et al. (2007) The MDM2 ubiquitination signal in the DNA-binding domain of p53 forms a docking site for calcium calmodulin kinase superfamily members. Mol Cell Biol 27, 3542-55
17339337   Curated Info

14

Vega FM, Sevilla A, Lazo PA (2004) p53 Stabilization and accumulation induced by human vaccinia-related kinase 1. Mol Cell Biol 24, 10366-80
15542844   Curated Info

15

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

16

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

17

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

18

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

19

Barcia R, López-Borges S, Vega FM, Lazo PA (2002) Kinetic properties of p53 phosphorylation by the human vaccinia-related kinase 1. Arch Biochem Biophys 399, 1-5
11883897   Curated Info

20

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

21

Dornan D, Hupp TR (2001) Inhibition of p53-dependent transcription by BOX-I phospho-peptide mimetics that bind to p300. EMBO Rep 2, 139-44
11258706   Curated Info

22

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

23

Webley K, et al. (2000) Posttranslational modifications of p53 in replicative senescence overlapping but distinct from those induced by DNA damage. Mol Cell Biol 20, 2803-8
10733583   Curated Info

24

Sakaguchi K, et al. (2000) Damage-mediated phosphorylation of human p53 threonine 18 through a cascade mediated by a casein 1-like kinase. Effect on Mdm2 binding. J Biol Chem 275, 9278-83
10734067   Curated Info

25

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

26

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