Lys120
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Home > Acetylation Site Page: > Lys120  -  p53 (human)

Site Information
FLhSGTAkSVTCTyS   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 474514

In vivo Characterization
Methods used to characterize site in vivo:
3H acetate labeling ( 32 ) , electrophoretic mobility shift ( 3 ) , flow cytometry ( 3 , 4 , 5 ) , immunoassay ( 13 , 24 ) , immunoprecipitation ( 2 , 3 , 4 , 5 , 6 , 10 , 20 , 21 , 23 , 24 , 25 , 31 , 33 , 38 ) , mass spectrometry ( 2 , 4 , 13 , 20 , 37 , 39 ) , mass spectrometry (in vitro) ( 14 , 28 ) , modification-specific antibody ( 3 , 7 , 10 , 11 , 13 , 14 , 16 , 17 , 18 , 21 , 22 , 23 , 24 , 25 , 27 , 29 , 31 , 32 , 33 , 38 , 39 ) , mutation of modification site ( 3 , 4 , 5 , 12 , 13 , 14 , 15 , 17 , 18 , 19 , 20 , 22 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 39 ) , phospho-antibody ( 19 , 31 ) , western blotting ( 2 , 3 , 4 , 5 , 7 , 10 , 11 , 13 , 14 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 27 , 29 , 31 , 32 , 38 , 39 )
Disease tissue studied:
bladder cancer ( 34 ) , bone cancer ( 3 , 4 , 6 , 12 , 14 , 16 , 20 , 21 , 22 , 25 , 33 , 38 ) , osteosarcoma ( 12 ) , brain cancer ( 34 ) , glioblastoma ( 34 ) , glioma ( 34 ) , breast cancer ( 13 , 24 , 31 , 33 , 39 ) , colorectal cancer ( 6 , 14 , 18 , 19 , 20 , 21 , 27 , 29 , 31 , 37 ) , colorectal carcinoma ( 6 , 14 , 18 , 19 , 20 , 21 , 27 , 29 , 31 , 37 ) , liver cancer ( 14 , 22 , 34 ) , lung cancer ( 3 , 5 , 6 , 13 , 14 , 15 , 18 , 20 , 21 , 25 , 30 , 31 , 32 , 33 , 36 , 37 , 39 ) , non-small cell lung cancer ( 3 , 5 , 6 , 13 , 14 , 15 , 18 , 20 , 21 , 25 , 30 , 31 , 32 , 33 , 36 , 37 , 39 ) , non-small cell lung adenocarcinoma ( 13 ) , ovarian cancer ( 10 ) , prostate cancer ( 29 , 33 , 39 ) , melanoma skin cancer ( 3 )
Relevant cell line - cell type - tissue:
'stem, embryonic' ( 17 ) , 293 (epithelial) ( 2 ) , A375 (melanocyte) ( 3 ) , A549 (pulmonary) ( 13 ) , BJ (fibroblast) ( 23 ) , BOSC ( 24 ) , DU 145 (prostate cell) ( 29 ) , E.coli (bacterial) ( 28 ) , EJ (bladder cell) ( 11 ) , HCT116 (intestinal) ( 6 , 14 , 18 , 19 , 20 , 21 , 27 , 29 , 31 , 37 ) , HEK293T (epithelial) ( 4 , 13 , 31 , 32 ) , HepG2 (hepatic) ( 22 , 34 ) , IEC-6 (epithelial) ( 7 ) , LNCaP (prostate cell) ( 29 , 33 , 39 ) , MCF-7 (breast cell) ( 13 , 24 , 31 , 33 , 39 ) , MEF (fibroblast) ( 3 , 24 ) , MEF-3T3 ( 13 ) , MHM (bone cell) ( 12 ) , NCI-H1299 (pulmonary) ( 3 , 5 , 6 , 13 , 14 , 15 , 18 , 20 , 21 , 25 , 30 , 31 , 32 , 33 , 36 , 37 , 39 ) , neuron ( 2 ) , OVISE (ovarian) ( 10 ) , OVTOKO (ovarian) ( 10 ) , PC3 (prostate cell) ( 29 ) , RMG1 (ovarian) ( 10 ) , Saos-2 (bone cell) ( 6 , 22 ) , SMMC7721 (hepatocyte) ( 14 ) , stem-colon ( 7 ) , T24 (bladder cell) ( 34 ) , TOV21G (ovarian) ( 10 ) , U2OS (bone cell) ( 3 , 4 , 12 , 14 , 16 , 20 , 21 , 22 , 25 , 33 , 38 ) , U87MG (glial) ( 34 )

Upstream Regulation
Regulatory protein:
BTG2 (human) ( 11 ) , CCDC8 (human) ( 25 ) , HRas (human) ( 23 ) , ING5 (human) ( 22 ) , MKK3 (human) ( 16 ) , MKK6 (human) ( 16 ) , MYST2 (human) ( 39 ) , MYST3 (human) ( 24 ) , Oct4 (human) ( 17 ) , p16-INK4A (human) ( 38 ) , P38A (human) ( 16 ) , P38B (human) ( 16 ) , PDCD5 (human) ( 22 ) , PML (human) ( 24 ) , RNF8 (human) ( 4 ) , Tip60 (human) ( 4 , 7 , 23 ) , TRIM29 (human) ( 27 ) , UHRF1 (human) ( 21 )
Treatments:
actinomycin_D ( 14 ) , ACY1215 ( 10 ) , adriamycin ( 16 , 22 ) , auranofin ( 7 ) , butyrate ( 13 ) , cisplatin ( 12 ) , CPT ( 18 ) , doxycycline ( 3 ) , etoposide ( 4 , 19 ) , ionizing_radiation ( 7 , 16 , 24 , 29 , 39 ) , KN-92 ( 19 ) , KN-93 ( 19 , 20 ) , linsitinib ( 12 ) , MS275 ( 31 ) , nicotinamide ( 3 , 21 , 25 , 37 ) , nutlin-3 ( 18 , 31 ) , retinoic_acid ( 17 ) , SB203580 ( 16 ) , siRNA ( 13 , 14 , 16 , 18 , 21 , 22 , 24 , 25 , 32 , 39 ) , tiron ( 19 ) , trichostatin_A ( 3 , 21 , 25 , 37 ) , UV ( 27 , 38 , 39 ) , valproic acid ( 29 )

Downstream Regulation
Effects of modification on p53:
acetylation ( 2 , 5 , 6 ) , activity, induced ( 14 , 17 ) , intracellular localization ( 20 , 30 ) , molecular association, regulation ( 6 , 13 , 17 , 18 , 22 , 28 , 39 ) , protein stabilization ( 17 )
Effects of modification on biological processes:
apoptosis, altered ( 6 ) , apoptosis, induced ( 2 , 4 , 7 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 18 , 19 , 20 , 21 , 22 , 25 , 27 , 29 , 31 , 32 , 33 , 37 , 39 ) , carcinogenesis, inhibited ( 11 , 27 ) , cell cycle regulation ( 39 ) , cell differentiation, induced ( 17 ) , cell growth, inhibited ( 1 , 11 , 21 , 27 ) , DNA repair, inhibited ( 4 ) , signaling pathway regulation ( 16 ) , transcription, altered ( 6 , 34 , 36 , 37 ) , transcription, induced ( 1 , 3 , 5 , 12 , 13 , 14 , 16 , 17 , 19 , 20 , 21 , 24 , 32 , 35 , 39 )
Induce interaction with:
DDX5 (human) ( 18 ) , DNA ( 13 , 18 , 22 , 28 , 39 )
Inhibit interaction with:
MDM2 (human) ( 17 )

Disease / Diagnostics Relevance
Relevant diseases:
ovarian cancer ( 10 )

References 

1

Phorl S, et al. (2022) Opposing roles of HDAC6 in liver regeneration and hepatocarcinogenesis. Cancer Sci 113, 2311-2322
35534985   Curated Info

2

Yoon JY, et al. (2022) Metabolic rescue ameliorates mitochondrial encephalo-cardiomyopathy in murine and human iPSC models of Leigh syndrome. Clin Transl Med 12, e954
35872650   Curated Info

3

Cao Z, et al. (2021) An unexpected role for p53 in regulating cancer cell-intrinsic PD-1 by acetylation. Sci Adv 7
33789902   Curated Info

4

Chen H, et al. (2020) RNF8 promotes efficient DSB repair by inhibiting the pro-apoptotic activity of p53 through regulating the function of Tip60. Cell Prolif 53, e12780
32031738   Curated Info

5

Wang Y, et al. (2020) The role of acetylation sites in the regulation of p53 activity. Mol Biol Rep 47, 381-391
31680191   Curated Info

6

Chen S, et al. (2019) iASPP mediates p53 selectivity through a modular mechanism fine-tuning DNA recognition. Proc Natl Acad Sci U S A 116, 17470-17479
31395738   Curated Info

7

Nag D, et al. (2019) Auranofin Protects Intestine against Radiation Injury by Modulating p53/p21 Pathway and Radiosensitizes Human Colon Tumor. Clin Cancer Res 25, 4791-4807
30940656   Curated Info

8

Lee SY, et al. (2019) K120R mutation inactivates p53 by creating an aberrant splice site leading to nonsense-mediated mRNA decay. Oncogene 38, 1597-1610
30348990   Curated Info

9

Luff SA, Kao CY, Papoutsakis ET (2018) Role of p53 and transcription-independent p53-induced apoptosis in shear-stimulated megakaryocytic maturation, particle generation, and platelet biogenesis. PLoS One
30231080   Curated Info

10

Bitler BG, et al. (2017) ARID1A-mutated ovarian cancers depend on HDAC6 activity. Nat Cell Biol 19, 962-973
28737768   Curated Info

11

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

12

Davaadelger B, et al. (2016) Crosstalk between the IGF-1R/AKT/mTORC1 pathway and the tumor suppressors p53 and p27 determines cisplatin sensitivity and limits the effectiveness of an IGF-1R pathway inhibitor. Oncotarget 7, 27511-26
27050276   Curated Info

13

Yun T, et al. (2016) Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway. J Biol Chem 291, 7386-95
26851285   Curated Info

14

Liu X, et al. (2016) NAT10 regulates p53 activation through acetylating p53 at K120 and ubiquitinating Mdm2. EMBO Rep 17, 349-66
26882543   Curated Info

15

Leszczynska KB, et al. (2015) Hypoxia-induced p53 modulates both apoptosis and radiosensitivity via AKT. J Clin Invest 125, 2385-98
25961455   Curated Info

16

Xu Y, et al. (2014) Phosphorylation of Tip60 by p38α regulates p53-mediated PUMA induction and apoptosis in response to DNA damage. Oncotarget 5, 12555-72
25544752   Curated Info

17

Zhang ZN, Chung SK, Xu Z, Xu Y (2014) Oct4 maintains the pluripotency of human embryonic stem cells by inactivating p53 through Sirt1-mediated deacetylation. Stem Cells 32, 157-65
24038750   Curated Info

18

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

19

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

20

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

21

Dai C, Shi D, Gu W (2013) Negative Regulation of the Acetyltransferase TIP60-p53 Interplay by UHRF1 (Ubiquitin-like with PHD and RING Finger Domains 1). J Biol Chem 288, 19581-92
23677994   Curated Info

22

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

23

Zheng H, et al. (2013) A Posttranslational Modification Cascade Involving p38, Tip60, and PRAK Mediates Oncogene-Induced Senescence. Mol Cell 50, 699-710
23685072   Curated Info

24

Rokudai S, et al. (2013) MOZ increases p53 acetylation and premature senescence through its complex formation with PML. Proc Natl Acad Sci U S A 110, 3895-900
23431171   Curated Info

25

Dai C, et al. (2011) Differential effects on p53-mediated cell cycle arrest vs. apoptosis by p90. Proc Natl Acad Sci U S A 108, 18937-42
22084066   Curated Info

26

Charvet C, et al. (2011) Phosphorylation of Tip60 by GSK-3 determines the induction of PUMA and apoptosis by p53. Mol Cell 42, 584-96
21658600   Curated Info

27

Sho T, et al. (2011) TRIM29 negatively regulates p53 via inhibition of Tip60. Biochim Biophys Acta 1813, 1245-53
21463657   Curated Info

28

Arbely E, et al. (2011) Acetylation of lysine 120 of p53 endows DNA-binding specificity at effective physiological salt concentration. Proc Natl Acad Sci U S A 108, 8251-6
21525412   Curated Info

29

Chen X, Wong JY, Wong P, Radany EH (2011) Low-dose valproic acid enhances radiosensitivity of prostate cancer through acetylated p53-dependent modulation of mitochondrial membrane potential and apoptosis. Mol Cancer Res 9, 448-61
21303901   Curated Info

30

Kuroda T, et al. (2011) RNA content in the nucleolus alters p53 acetylation via MYBBP1A. EMBO J 30, 1054-66
21297583   Curated Info

31

Mellert HS, et al. (2011) Deacetylation of the DNA-binding domain regulates p53-mediated apoptosis. J Biol Chem 286, 4264-70
21148320   Curated Info

32

Li X, et al. (2009) Two mammalian MOF complexes regulate transcription activation by distinct mechanisms. Mol Cell 36, 290-301
19854137   Curated Info

33

Sykes SM, et al. (2009) Acetylation of the DNA binding domain regulates transcription-independent apoptosis by p53. J Biol Chem 284, 20197-205
19494119   Curated Info

34

Shinmen N, et al. (2009) Activation of NFAT signal by p53-K120R mutant. FEBS Lett 583, 1916-22
19416725   Curated Info

35

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

36

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

37

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

38

Mellert H, Sykes SM, Murphy ME, McMahon SB (2007) The ARF/oncogene pathway activates p53 acetylation within the DNA binding domain. Cell Cycle 6, 1304-6
17534149   Curated Info

39

Sykes SM, et al. (2006) Acetylation of the p53 DNA-binding domain regulates apoptosis induction. Mol Cell 24, 841-51
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