Regulation of TP53 Activity through Methylation

Adams CJ, Pike ACW, Maniam S, Sharpe TD, Coutts AS, Knapp S, La Thangue NB, Bullock AN. The p53 cofactor Strap exhibits an unexpected TPR motif and oligonucleotide-binding (OB)–fold structure. Proc. Natl. Acad. Sci. U.S.A. 2012 Feb 23;109(10):3778–83. doi: 10.1073/pnas.1113731109.; Bai Q, Shen Y, Yao X, Wang F, Du Y, Wang Q, Jin N, Hai J, Hu T, Yang J. Modeling a New Water Channel That Allows SET9 to Dimethylate p53. PLoS ONE. 2011 May 19;6(5):e19856. doi: 10.1371/journal.pone.0019856.; West LE, Roy S, Lachmi-Weiner K, Hayashi R, Shi X, Appella E, Kutateladze TG, Gozani O. The MBT Repeats of L3MBTL1 Link SET8-mediated p53 Methylation at Lysine 382 to Target Gene Repression. Journal of Biological Chemistry. 2010 Nov;285(48):37725–32. doi: 10.1074/jbc.m110.139527.; Huang J, Dorsey J, Chuikov S, Zhang X, Jenuwein T, Reinberg D, Berger SL. G9a and Glp Methylate Lysine 373 in the Tumor Suppressor p53. Journal of Biological Chemistry. 2010 Mar;285(13):9636–41. doi: 10.1074/jbc.m109.062588.; Adams CJ, Graham AL, Jansson M, Coutts AS, Edelmann M, Smith L, Kessler B, La Thangue NB. ATM and Chk2 kinase target the p53 cofactor Strap. EMBO Reports. 2008 Oct 03;9(12):1222–9. doi: 10.1038/embor.2008.186.; Huang J, Sengupta R, Espejo AB, Lee MG, Dorsey JA, Richter M, Opravil S, Shiekhattar R, Bedford MT, Jenuwein T, Berger SL. p53 is regulated by the lysine demethylase LSD1. Nature. 2007 Sep 06;449(7158):105–8. doi: 10.1038/nature06092. PMID: 17805299.; Huang J, Perez-Burgos L, Placek BJ, Sengupta R, Richter M, Dorsey JA, Kubicek S, Opravil S, Jenuwein T, Berger SL. Repression of p53 activity by Smyd2-mediated methylation. Nature. 2006 Nov 30;444(7119):629–32. doi: 10.1038/nature05287. PMID: 17108971.; Couture J, Collazo E, Hauk G, Trievel RC. Structural basis for the methylation site specificity of SET7/9. Nature Structural & Molecular Biology. 2006 Jan 15;13(2):140–6. doi: 10.1038/nsmb1045.; Chuikov S, Kurash JK, Wilson JR, Xiao B, Justin N, Ivanov GS, McKinney K, Tempst P, Prives C, Gamblin SJ, Barlev NA, Reinberg D. Regulation of p53 activity through lysine methylation. Nature. 2004 Nov 18;432(7015):353–60. doi: 10.1038/nature03117. PMID: 15525938.; Demonacos C, Krstic-Demonacos M, Smith L, Xu D, O'Connor DP, Jansson M, La Thangue NB. A new effector pathway links ATM kinase with the DNA damage response. Nat Cell Biol. 2004 Oct;6(10):968–76. doi: 10.1038/ncb1170. PMID: 15448695.; An W, Kim J, Roeder RG. Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53. Cell. 2004 Jun 11;117(6):735–48. doi: 10.1016/j.cell.2004.05.009. PMID: 15186775.; Demonacos C, Krstic-Demonacos M, La Thangue NB. A TPR motif cofactor contributes to p300 activity in the p53 response. Mol Cell. 2001 Jul;8(1):71–84. doi: 10.1016/s1097-2765(01)00277-5. PMID: 11511361.; Shikama N, Lee CW, France S, Delavaine L, Lyon J, Krstic-Demonacos M, La Thangue NB. A novel cofactor for p300 that regulates the p53 response. Mol Cell. 1999 Sep;4(3):365–76. doi: 10.1016/s1097-2765(00)80338-x. PMID: 10518217.

Metabolites

ATP(4-)

Formula: C10H12N5O13P3 (502.9644492)

CAS ID:

ADP(3-)

Formula: C10H12N5O10P2 (424.0059412)

CAS ID:



Enzyme

EC Number name full name note
2.3.2.27 RING-type E3 ubiquitin transferase [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (isopeptide bond-forming; RING-type)


Proteins

Protein ID name full name