Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity

Cell
Dimitris P XirodimasDavid P Lane

Abstract

The only reported role for the conjugation of the NEDD8 ubiquitin-like molecule is control of the activity of SCF ubiquitin ligase complexes. Here, we show that the Mdm2 RING finger E3 ubiquitin ligase can also promote NEDD8 modification of the p53 tumor suppressor protein. Mdm2 is itself modified with NEDD8 with very similar characteristics to the autoubiquitination activity of Mdm2. By using a cell line (TS-41) with a temperature-sensitive mutation in the NEDD8 conjugation pathway and a p53 mutant that cannot be NEDDylated (3NKR), we demonstrate that Mdm2-dependent NEDD8 modification of p53 inhibits its transcriptional activity. These findings expand the role for Mdm2 as an E3 ligase, providing evidence that Mdm2 is a common component of the ubiquitin and NEDD8 conjugation pathway and indicating the diverse mechanisms by which E3 ligases can control the function of substrate proteins.

References

Jul 1, 1993·Molecular and Cellular Biology·J ChenA J Levine
May 15, 1997·Nature·Y HauptM Oren
May 15, 1997·Nature·M H KubbutatK H Vousden
May 26, 1998·The EMBO Journal·D LiakopoulosS Jentsch
Aug 8, 1998·Genes & Development·F OsakaS Kato
Dec 19, 1998·The EMBO Journal·A Ciechanover
Apr 17, 1999·The Journal of Biological Chemistry·L Gong, E T Yeh
Nov 24, 1999·The EMBO Journal·M S RodriguezR T Hay
Dec 28, 1999·Annual Review of Cell and Developmental Biology·R J Deshaies
Mar 18, 2000·The Journal of Biological Chemistry·S FangA M Weissman
Jun 3, 2000·Annual Review of Immunology·M Karin, Y Ben-Neriah
Oct 25, 2000·Molecular and Cellular Biology·M S RodriguezR T Hay
Mar 10, 2001·Experimental Cell Research·K Kondo, W G Kaelin
Mar 27, 2001·Nature Reviews. Molecular Cell Biology·A M Weissman
Aug 3, 2001·The EMBO Journal·T KawakamiK Tanaka
Oct 19, 2001·EMBO Reports·R StadA G Jochemsen
Apr 19, 2002·Biochimica Et Biophysica Acta·Karen H Vousden
Sep 7, 2002·The Plant Cell·William M GrayMark Estelle
Sep 26, 2002·FEBS Letters·Dimitris P XirodimasRonald T Hay
Jan 1, 2003·Seminars in Cancer Biology·Joanna Bloom, Michele Pagano
Jan 1, 2003·Seminars in Cancer Biology·Dan Michael, Moshe Oren
Jan 2, 2003·Molecular and Cellular Biology·Susan M MendrysaMary Ellen Perry
Feb 5, 2003·Biochemical and Biophysical Research Communications·Mitsuru MorimotoHideyo Yasuda

❮ Previous
Next ❯

Citations

Jun 15, 2005·Journal of Molecular Biology·Stanislava UhrinovaPaul N Barlow
Feb 6, 2008·Journal of Proteome Research·Jeffrey JonesLan Huang
Mar 15, 2008·Cell Death and Differentiation·M X GaoW B Derry
Apr 10, 2010·Cell Death and Differentiation·L CollavinG Del Sal
Dec 4, 2004·Nature·Chaowei WuKonstantin Galaktionov
Mar 21, 2007·Nature Cell Biology·Stephanie CarterKaren H Vousden
Sep 5, 2009·Nature Protocols·Michael H TathamRonald T Hay
Oct 29, 2004·Nature Reviews. Cancer·Ann M Bode, Zigang Dong
Sep 23, 2006·Nature Reviews. Cancer·Daniela HoellerIvan Dikic
Jul 4, 2006·Nature Reviews. Drug Discovery·Grzegorz NalepaJ Wade Harper
Apr 2, 2005·Nature Reviews. Molecular Cell Biology·David L Vaux, John Silke
Aug 3, 2005·Nature Reviews. Molecular Cell Biology·Rebecca L WelchmanR John Mayer
Aug 23, 2008·Nature Reviews. Molecular Cell Biology·Fiona Murray-ZmijewskiXin Lu
Feb 12, 2008·Nature Structural & Molecular Biology·Danny T HuangBrenda A Schulman
Sep 29, 2004·Nature Structural & Molecular Biology·Andrew P VanDemark, Christopher P Hill
Nov 7, 2007·Nature Structural & Molecular Biology·John A Latham, Sharon Y R Dent
Sep 29, 2009·Oncogene·I R WatsonM S Irwin
Feb 27, 2007·Oncogene·H F Horn, K H Vousden
Apr 3, 2007·Oncogene·T Iwakuma, G Lozano
Jul 21, 2009·Proceedings of the National Academy of Sciences of the United States of America·Nathalie Meyer-SchallerMatthias Peter
Jan 5, 2011·The Journal of Biological Chemistry·Ji-Hye RyuYang-Sook Chun
Nov 14, 2006·The Journal of Biological Chemistry·Wassim M AbidaWei Gu
Feb 27, 2014·Biotechnology & Genetic Engineering Reviews·Guoqiang Xu, Samie R Jaffrey
Oct 13, 2010·The Journal of Experimental Medicine·Francis A FlomerfeltRonald E Gress
Sep 16, 2005·Molecular Biology of the Cell·Yutaka MoritaShunsuke Ishii
Apr 9, 2011·Carcinogenesis·Keita NoguchiShigetsugu Hatakeyama
Apr 17, 2012·Carcinogenesis·Lisa M Miller JenkinsEttore Appella
Mar 6, 2012·Human Molecular Genetics·Yeun Su ChooZhuohua Zhang
May 12, 2010·Cold Spring Harbor Perspectives in Biology·David W Meek, Carl W Anderson
Sep 1, 2005·Genes & Development·Jean-Christophe BourdonDavid P Lane
Jul 28, 2006·Cold Spring Harbor Symposia on Quantitative Biology·D P Lane
Apr 30, 2011·Plant Physiology·Jana Pia HakenjosClaus Schwechheimer
Aug 2, 2013·Plant Physiology·Jana P HakenjosClaus Schwechheimer
Aug 12, 2004·Science's STKE : Signal Transduction Knowledge Environment·Olivier Staub
Sep 27, 2006·Molecular and Cellular Biology·Aaron LaineZe'ev Ronai
Feb 20, 2008·Biochemistry. Biokhimii︠a︡·P M Chumakov
Mar 10, 2010·Biochemistry. Biokhimii︠a︡·A V SorokinL P Ovchinnikov

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell eTOC

Cell is a scientific journal publishing research across a broad range of disciplines within the life sciences field. Discover the latest research from Cell here.