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  MDM2 recruitment of lysine methyltransferases regulates p53 transcriptional output

Chen, L., Li, Z., Zwolinska, A. K., Smith, M. A., Cross, B., Koomen, J., et al. (2010). MDM2 recruitment of lysine methyltransferases regulates p53 transcriptional output. The EMBO Journal, 29, 2538-2552.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-8EA9-D Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-8EAA-B
Genre: Journal Article

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 Creators:
Chen, Lihong, Author
Li, Zhenyu, Author
Zwolinska, Aleksandra K., Author
Smith, Matthew A., Author
Cross, Brittany, Author
Koomen, John, Author
Yuan, Zhi-Min, Author
Jenuwein, Thomas1, Author              
Marine, Jean-Christophe, Author
Wright, Kenneth L., Author
Chen, Jiandong, Author
Affiliations:
1Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243644              

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Free keywords: EHMT1; histone methyltransferases; MDM2; p53; SUV39H1
 Abstract: MDM2 is a key regulator of the p53 tumor suppressor acting primarily as an E3 ubiquitin ligase to promote its degradation. MDM2 also inhibits p53 transcriptional activity by recruiting histone deacetylase and corepressors to p53. Here, we show that immunopurified MDM2 complexes have significant histone H3-K9 methyltransferase activity. The histone methyltransferases SUV39H1 and EHMT1 bind specifically to MDM2 but not to its homolog MDMX. MDM2 mediates formation of p53-SUV39H1/EHMT1 complex capable of methylating H3-K9 in vitro and on p53 target promoters in vivo. Furthermore, MDM2 promotes EHMT1-mediated p53 methylation at K373. Knockdown of SUV39H1 and EHMT1 increases p53 activity during stress response without affecting p53 levels, whereas their overexpression inhibits p53 in an MDM2-dependent manner. The p53 activator ARF inhibits SUV39H1 and EHMT1 binding to MDM2 and reduces MDM2-associated methyltransferase activity. These results suggest that MDM2-dependent recruitment of methyltransferases is a novel mechanism of p53 regulation through methylation of both p53 itself and histone H3 at target promoters.

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Language(s): eng - English
 Dates: 2010
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 527607
 Degree: -

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Title: The EMBO Journal
Source Genre: Journal
 Creator(s):
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Publ. Info: -
Pages: - Volume / Issue: 29 Sequence Number: - Start / End Page: 2538 - 2552 Identifier: -