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3oq5

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Template:STRUCTURE 3oq5

Contents

Crystal structure of the 3-MBT domain from human L3MBTL1 in complex with p53K382me1

Template:ABSTRACT PUBMED 20870725

Function

[LMBL1_HUMAN] Polycomb group (PcG) protein that specifically recognizes and binds mono- and dimethyllysine residues on target proteins, therey acting as a 'reader' of a network of post-translational modifications. PcG proteins maintain the transcriptionally repressive state of genes: acts as a chromatin compaction factor by recognizing and binding mono- and dimethylated histone H1b/HIST1H1E at 'Lys-26' (H1bK26me1 and H1bK26me2) and histone H4 at 'Lys-20' (H4K20me1 and H4K20me2), leading to condense chromatin and repress transcription. Recognizes and binds p53/TP53 monomethylated at 'Lys-382', leading to repress p53/TP53-target genes. Also recognizes and binds RB1/RB monomethylated at 'Lys-860'. Participates in the ETV6-mediated repression. Probably plays a role in cell proliferation. Overexpression induces multinucleated cells, suggesting that it is required to accomplish normal mitosis.[1][2][3][4] [Q5U0E4_HUMAN] Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression (By similarity).[RuleBase:RU003304]

About this Structure

3oq5 is a 5 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  • 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. J Biol Chem. 2010 Sep 24. PMID:20870725 doi:10.1074/jbc.M110.139527
  1. ↑ Trojer P, Li G, Sims RJ 3rd, Vaquero A, Kalakonda N, Boccuni P, Lee D, Erdjument-Bromage H, Tempst P, Nimer SD, Wang YH, Reinberg D. L3MBTL1, a histone-methylation-dependent chromatin lock. Cell. 2007 Jun 1;129(5):915-28. PMID:17540172 doi:10.1016/j.cell.2007.03.048
  2. ↑ Kalakonda N, Fischle W, Boccuni P, Gurvich N, Hoya-Arias R, Zhao X, Miyata Y, Macgrogan D, Zhang J, Sims JK, Rice JC, Nimer SD. Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1. Oncogene. 2008 Jul 17;27(31):4293-304. doi: 10.1038/onc.2008.67. Epub 2008 Apr, 14. PMID:18408754 doi:10.1038/onc.2008.67
  3. ↑ Saddic LA, West LE, Aslanian A, Yates JR 3rd, Rubin SM, Gozani O, Sage J. Methylation of the retinoblastoma tumor suppressor by SMYD2. J Biol Chem. 2010 Nov 26;285(48):37733-40. doi: 10.1074/jbc.M110.137612. Epub, 2010 Sep 24. PMID:20870719 doi:10.1074/jbc.M110.137612
  4. ↑ 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. J Biol Chem. 2010 Sep 24. PMID:20870725 doi:10.1074/jbc.M110.139527

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