Lys373
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Home > Acetylation Site Page: > Lys373  -  p53 (human)

Site Information
sSHLkskkGQstsRH   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 458980

In vivo Characterization
Methods used to characterize site in vivo:
immunoprecipitation ( 5 , 9 , 39 , 40 , 54 ) , mass spectrometry ( 37 , 63 ) , microscopy-colocalization with upstream kinase ( 5 ) , modification-specific antibody ( 22 , 39 , 54 ) , mutation of modification site ( 9 , 31 , 37 , 39 , 40 , 59 , 61 ) , phospho-antibody ( 5 , 13 , 51 , 54 ) , western blotting ( 5 , 13 , 22 , 39 , 40 , 51 , 54 )
Disease tissue studied:
bone cancer ( 5 , 9 , 39 ) , breast cancer ( 59 ) , colorectal cancer ( 13 , 22 , 37 , 40 , 54 ) , colorectal carcinoma ( 13 , 22 , 37 , 40 , 54 ) , leukemia ( 63 ) , acute myelogenous leukemia ( 63 ) , lung cancer ( 5 , 31 , 37 , 39 , 61 ) , non-small cell lung cancer ( 5 , 31 , 37 , 39 , 61 )
Relevant cell line - cell type - tissue:

Upstream Regulation
Regulatory protein:
TWIST1 (human) ( 22 )
Treatments:
adriamycin ( 5 ) , camptothecin ( 16 ) , DDATHF ( 54 ) , etoposide ( 40 , 54 ) , nicotinamide ( 37 ) , trichostatin_A ( 37 , 39 ) , UV ( 39 , 40 )

Downstream Regulation
Effects of modification on p53:
molecular association, regulation ( 39 ) , protein degradation ( 59 , 61 ) , ubiquitination ( 61 )
Effects of modification on biological processes:
apoptosis, induced ( 37 ) , cell growth, induced ( 59 ) , transcription, altered ( 31 , 37 ) , transcription, induced ( 39 )
Induce interaction with:
DNA ( 39 ) , TAF1 (human) ( 39 )

References 

1

Zheng S, et al. (2017) Inhibiting p53 Acetylation Reduces Cancer Chemotoxicity. Cancer Res 77, 4342-4354
28655792   Curated Info

2

Bao L, et al. (2016) Histone deacetylase inhibitor induces cell apoptosis and cycle arrest in lung cancer cells via mitochondrial injury and p53 up-acetylation. Cell Biol Toxicol 32, 469-482
27423454   Curated Info

3

Choi OR, Ryu MS, Lim IK (2016) Shifting p53-induced senescence to cell death by TIS21(/BTG2/Pc3) gene through posttranslational modification of p53 protein. Cell Signal 28, 1172-85
27208501   Curated Info

4

Li Z, et al. (2016) USP4 inhibits p53 and NF-κB through deubiquitinating and stabilizing HDAC2. Oncogene 35, 2902-12
26411366   Curated Info

5

Conrad E, et al. (2016) HIPK2 restricts SIRT1 activity upon severe DNA damage by a phosphorylation-controlled mechanism. Cell Death Differ 23, 110-22
26113041   Curated Info

6

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

7

Zhao B, et al. (2015) Connexin32 regulates hepatoma cell metastasis and proliferation via the p53 and Akt pathways. Oncotarget 6, 10116-33
25426556   Curated Info

8

Liu L, et al. (2014) Exogenous NAD(+) supplementation protects H9c2 cardiac myoblasts against hypoxia/reoxygenation injury via Sirt1-p53 pathway. Fundam Clin Pharmacol 28, 180-9
23384296   Curated Info

9

Wu Y, et al. (2014) Phosphorylation of p53 by TAF1 inactivates p53-dependent transcription in the DNA damage response. Mol Cell 53, 63-74
24289924   Curated Info

10

Shan X, et al. (2014) Ginsenoside Rg3 Inhibits Melanoma Cell Proliferation through Down-Regulation of Histone Deacetylase 3 (HDAC3) and Increase of p53 Acetylation. PLoS One 9, e115401
25521755   Curated Info

11

Chang J, et al. (2013) Acetylation of p53 stimulates miRNA processing and determines cell survival following genotoxic stress. EMBO J 32, 3192-205
24219989   Curated Info

12

Wu J, et al. (2013) The up-regulation of histone deacetylase 8 promotes proliferation and inhibits apoptosis in hepatocellular carcinoma. Dig Dis Sci 58, 3545-53
24077923   Curated Info

13

Sen N, Kumari R, Singh MI, Das S (2013) HDAC5, a key component in temporal regulation of p53-mediated transactivation in response to genotoxic stress. Mol Cell 52, 406-20
24120667   Curated Info

14

Kim SS, Benchimol S (2013) HDAC5--a critical player in the p53 acetylation network. Mol Cell 52, 289-90
24207022   Curated Info

15

Liu N, et al. (2013) ING5 Is a Tip60 Cofactor That Acetylates p53 in Response to DNA Damage. Cancer Res 73, 3749-60
23576563   Curated Info

16

Brochier C, et al. (2013) Specific acetylation of p53 by HDAC inhibition prevents DNA damage-induced apoptosis in neurons. J Neurosci 33, 8621-32
23678107   Curated Info

17

Chan C, et al. (2013) Altered Binding Site Selection of p53 Transcription Cassettes by Hepatitis B Virus X Protein. Mol Cell Biol 33, 485-97
23149944   Curated Info

18

Wu D, et al. (2013) Runt-related Transcription Factor 1 (RUNX1) Stimulates Tumor Suppressor p53 Protein in Response to DNA Damage through Complex Formation and Acetylation. J Biol Chem 288, 1353-64
23148227   Curated Info

19

Knowell AE, et al. (2013) Id4 dependent acetylation restores mutant-p53 transcriptional activity. Mol Cancer 12, 161
24330748   Curated Info

20

Han X, et al. (2012) 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside ameliorates vascular senescence and improves blood flow involving a mechanism of p53 deacetylation. Atherosclerosis 225, 76-82
22981429   Curated Info

21

Kim K, et al. (2012) Functional interplay between p53 acetylation and H1.2 phosphorylation in p53-regulated transcription. Oncogene 31, 4290-301
22249259   Curated Info

22

Piccinin S, et al. (2012) A "Twist box" Code of p53 Inactivation: Twist box:p53 Interaction Promotes p53 Degradation. Cancer Cell 22, 404-15
22975381   Curated Info

23

Kim WJ, Rivera MN, Coffman EJ, Haber DA (2012) The WTX tumor suppressor enhances p53 acetylation by CBP/p300. Mol Cell 45, 587-97
22285752   Curated Info

24

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

25

Wu ZZ, Sun NK, Chao CC (2011) Knockdown of CITED2 using short-hairpin RNA sensitizes cancer cells to cisplatin through stabilization of p53 and enhancement of p53-dependent apoptosis. J Cell Physiol 226, 2415-28
21660965   Curated Info

26

Seo SK, et al. (2011) Histone deacetylase inhibitors sensitize human non-small cell lung cancer cells to ionizing radiation through acetyl p53-mediated c-myc down-regulation. J Thorac Oncol 6, 1313-9
21642861   Curated Info

27

Gaub P, et al. (2010) HDAC inhibition promotes neuronal outgrowth and counteracts growth cone collapse through CBP/p300 and P/CAF-dependent p53 acetylation. Cell Death Differ 17, 1392-408
20094059   Curated Info

28

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

29

Ravindra KC, et al. (2009) Inhibition of lysine acetyltransferase KAT3B/p300 activity by a naturally occurring hydroxynaphthoquinone, plumbagin. J Biol Chem 284, 24453-64
19570987   Curated Info

30

Wu SY, Chiang CM (2009) Crosstalk between sumoylation and acetylation regulates p53-dependent chromatin transcription and DNA binding. EMBO J 28, 1246-59
19339993   Curated Info

31

Tian C, et al. (2009) KRAB-type zinc-finger protein Apak specifically regulates p53-dependent apoptosis. Nat Cell Biol 11, 580-91
19377469   Curated Info

32

Yamaguchi H, et al. (2009) p53 Acetylation Is Crucial for Its Transcription-independent Proapoptotic Functions. J Biol Chem 284, 11171-83
19265193   Curated Info

33

Itahana Y, Ke H, Zhang Y (2009) p53 Oligomerization is essential for its C-terminal lysine acetylation. J Biol Chem 284, 5158-64
19106109   Curated Info

34

Zhu Z, et al. (2009) Human inhibitor of growth 1 inhibits hepatoma cell growth and influences p53 stability in a variant-dependent manner. Hepatology 49, 504-12
19085961   Curated Info

35

Yang W, Wetterskog D, Matsumoto Y, Funa K (2008) Kinetics of repression by modified p53 on the PDGF beta-receptor promoter. Int J Cancer 123, 2020-30
18697203   Curated Info

36

Chen JJ, Chou CW, Chang YF, Chen CC (2008) Proteasome inhibitors enhance TRAIL-induced apoptosis through the intronic regulation of DR5: involvement of NF-kappaB and reactive oxygen species-mediated p53 activation. J Immunol 180, 8030-9
18523266   Curated Info

37

Tang Y, et al. (2008) Acetylation is indispensable for p53 activation. Cell 133, 612-26
18485870   Curated Info

38

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

39

Li AG, et al. (2007) An acetylation switch in p53 mediates holo-TFIID recruitment. Mol Cell 28, 408-21
17996705   Curated Info

40

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

41

Ivanov GS, et al. (2007) Methylation-acetylation interplay activates p53 in response to DNA damage. Mol Cell Biol 27, 6756-69
17646389   Curated Info

42

Higashitsuji H, et al. (2007) Enhanced deacetylation of p53 by the anti-apoptotic protein HSCO in association with histone deacetylase 1. J Biol Chem 282, 13716-25
17353187   Curated Info

43

Nag A, et al. (2007) An essential role of human Ada3 in p53 acetylation. J Biol Chem 282, 8812-20
17272277   Curated Info

44

Roy S, Tenniswood M (2007) Site-specific acetylation of p53 directs selective transcription complex assembly. J Biol Chem 282, 4765-71
17121856   Curated Info

45

Singh K, et al. (2007) p53 target gene SMAR1 is dysregulated in breast cancer: its role in cancer cell migration and invasion. PLoS One 2, e660
17668048   Curated Info

46

Li AG, et al. (2006) Mechanistic insights into maintenance of high p53 acetylation by PTEN. Mol Cell 23, 575-87
16916644   Curated Info

47

Knights CD, et al. (2006) Distinct p53 acetylation cassettes differentially influence gene-expression patterns and cell fate. J Cell Biol 173, 533-44
16717128   Curated Info

48

Zhao Y, et al. (2006) Acetylation of p53 at lysine 373/382 by the histone deacetylase inhibitor depsipeptide induces expression of p21(Waf1/Cip1). Mol Cell Biol 26, 2782-90
16537920   Curated Info

49

Kawaguchi Y, Ito A, Appella E, Yao TP (2006) Charge modification at multiple C-terminal lysine residues regulates p53 oligomerization and its nucleus-cytoplasm trafficking. J Biol Chem 281, 1394-400
16291740   Curated Info

50

Roy S, Packman K, Jeffrey R, Tenniswood M (2005) Histone deacetylase inhibitors differentially stabilize acetylated p53 and induce cell cycle arrest or apoptosis in prostate cancer cells. Cell Death Differ 12, 482-91
15746940   Curated Info

51

Warnock LJ, Raines SA, Mee TR, Milner J (2005) Role of phosphorylation in p53 acetylation and PAb421 epitope recognition in baculoviral and mammalian expressed proteins. FEBS J 272, 1669-75
15794754   Curated Info

52

Luo J, et al. (2004) Acetylation of p53 augments its site-specific DNA binding both in vitro and in vivo. Proc Natl Acad Sci U S A 101, 2259-64
14982997   Curated Info

53

Mujtaba S, et al. (2004) Structural mechanism of the bromodomain of the coactivator CBP in p53 transcriptional activation. Mol Cell 13, 251-63
14759370   Curated Info

54

Bronder JL, Moran RG (2003) A defect in the p53 response pathway induced by de novo purine synthesis inhibition. J Biol Chem 278, 48861-71
14517211   Curated Info

55

Kataoka H, et al. (2003) ING1 represses transcription by direct DNA binding and through effects on p53. Cancer Res 63, 5785-92
14522900   Curated Info

56

Zeng L, et al. (2003) The role of p53 deacetylation in p21Waf1 regulation by laminar flow. J Biol Chem 278, 24594-9
12716906   Curated Info

57

Harrod R, et al. (2003) Human immunodeficiency virus type-1 Tat/co-activator acetyltransferase interactions inhibit p53Lys-320 acetylation and p53-responsive transcription. J Biol Chem 278, 12310-8
12501250   Curated Info

58

Ito A, et al. (2002) MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation. EMBO J 21, 6236-45
12426395   Curated Info

59

Nakamura S, Roth JA, Mukhopadhyay T (2002) Multiple lysine mutations in the C-terminus of p53 make it resistant to degradation mediated by MDM2 but not by human papillomavirus E6 and induce growth inhibition in MDM2-overexpressing cells. Oncogene 21, 2605-10
11971195   Curated Info

60

Ito A, et al. (2001) p300/CBP-mediated p53 acetylation is commonly induced by p53-activating agents and inhibited by MDM2. EMBO J 20, 1331-40
11250899   Curated Info

61

Nakamura S, Roth JA, Mukhopadhyay T (2000) Multiple lysine mutations in the C-terminal domain of p53 interfere with MDM2-dependent protein degradation and ubiquitination. Mol Cell Biol 20, 9391-8
11094089   Curated Info

62

Luo J, et al. (2000) Deacetylation of p53 modulates its effect on cell growth and apoptosis. Nature 408, 377-81
11099047   Curated Info

63

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

64

Liu L, et al. (1999) p53 sites acetylated in vitro by PCAF and p300 are acetylated in vivo in response to DNA damage. Mol Cell Biol 19, 1202-9
9891054   Curated Info

65

Gu W, Roeder RG (1997) Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell 90, 595-606
9288740   Curated Info