HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 3, 1797-1804, January 19, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/3/1797    most recent M609001200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Abida, W. M. Articles by Gu, W. Search for Related Content PubMed PubMed Citation Articles by Abida, W. M. Articles by Gu, W. Social Bookmarking                      What's this?

FBXO11 Promotes the Neddylation of p53 and Inhibits Its Transcriptional Activity^*

From the Institute for Cancer Genetics and the Department of Pathology, College of Physicians & Surgeons, Columbia University, New York, New York 10032

The p53 tumor suppressor is regulated by post-translational modification, including ubiquitination, phosphorylation and acetylation. It has previously been shown that the ubiquitin ligase Mdm2 also promotes the conjugation of Nedd8, a ubiquitin-like protein, to p53, inhibiting its transcriptional activity. We report the identification of FBXO11, a member of the F-box protein family and a component of the Skp1·Cullin1·F-box (SCF) complex, as a new p53-interacting protein. We show that FBXO11 promotes the neddylation of p53 both in vitro and in vivo. In addition to the C-terminal lysine residues, FBXO11 can also promote Nedd8 conjugation to Lys-320 and Lys-321, and neddylation of p53 leads to suppression of p53 function. This is consistent with recent studies showing that a lysine to arginine mutation at Lys-320 significantly enhances p53 function, although Lys-320 was originally identified as an acetylation site involving PCAF-mediated activation of p53. Our study provides an example of an F-box protein acting as an adaptor protein that can mediate the neddylation of a non-cullin substrate.

Received for publication, September 21, 2006 , and in revised form, November 8, 2006.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY827075 [GenBank] .

^* This work was supported in part by grants from the NCI, National Institutes of Health (to W. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Present address: Genentech, 1 DNA Way, South San Francisco, CA 94080.

² To whom correspondence should be addressed: Irving Cancer Research Center, Rm. 609A, Inst. for Cancer Genetics, Columbia University, 1130 Saint Nicholas Ave., New York, NY 10032. Tel.: 212-851-5282; Fax: 212-851-5284; E-mail: wg8{at}columbia.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				L. M. Miller Jenkins, S. J. Mazur, M. Rossi, O. Gaidarenko, Y. Xu, and E. Appella Quantitative Proteomics Analysis of the Effects of Ionizing Radiation in Wild Type and p53K317R Knock-in Mouse Thymocytes Mol. Cell. Proteomics, April 1, 2008; 7(4): 716 - 727. [Abstract] [Full Text] [PDF]

				H. Wang, Y. Zhao, L. Li, M. A. McNutt, L. Wu, S. Lu, Y. Yu, W. Zhou, J. Feng, G. Chai, et al. 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., February 1, 2008; 283(5): 2564 - 2574. [Abstract] [Full Text] [PDF]

				J. Herrmann, L. O. Lerman, and A. Lerman Ubiquitin and Ubiquitin-Like Proteins in Protein Regulation Circ. Res., May 11, 2007; 100(9): 1276 - 1291. [Abstract] [Full Text] [PDF]