Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     


Originally published In Press as doi:10.1074/jbc.M706505200 on August 29, 2007

J. Biol. Chem., Vol. 282, Issue 47, 34167-34175, November 23, 2007
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
282/47/34167    most recent
M706505200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Uzunova, K.
Right arrow Articles by Dohmen, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Uzunova, K.
Right arrow Articles by Dohmen, R. J.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Ubiquitin-dependent Proteolytic Control of SUMO Conjugates*Formula

Kristina Uzunova{ddagger}1, Kerstin Göttsche{ddagger}, Maria Miteva{ddagger}2, Stefan R. Weisshaar{ddagger}§, Christoph Glanemann{ddagger}3, Marion Schnellhardt{ddagger}, Michaela Niessen{ddagger}, Hartmut Scheel, Kay Hofmann, Erica S. Johnson||, Gerrit J. K. Praefcke{ddagger}§, and R. Jürgen Dohmen{ddagger}4

From the {ddagger}Institute for Genetics, University of Cologne, Zülpicher Strasse 47, D-50674 Cologne, Germany, the §Center for Molecular Medicine Cologne, University of Cologne, Zülpicher Strasse 47, D-50674 Cologne, Germany, the Bioinformatics Department, Miltenyi Biotec GmbH, MACSmolecular Business Unit, Nattermannallee 1, D-50829 Cologne, Germany, and the ||Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Posttranslational protein modification with small ubiquitin-related modifier (SUMO) is an important regulatory mechanism implicated in many cellular processes, including several of biomedical relevance. We report that inhibition of the proteasome leads to accumulation of proteins that are simultaneously conjugated to both SUMO and ubiquitin in yeast and in human cells. A similar accumulation of such conjugates was detected in Saccharomyces cerevisiae ubc4 ubc5 cells as well as in mutants lacking two RING finger proteins, Ris1 and Hex3/Slx5-Slx8, that bind to SUMO as well as to the ubiquitin-conjugating enzyme Ubc4. In vitro, Hex3-Slx8 complexes promote Ubc4-dependent ubiquitylation. Together these data identify a previously unrecognized pathway that mediates the proteolytic down-regulation of sumoylated proteins. Formation of substrate-linked SUMO chains promotes targeting of SUMO-modified substrates for ubiquitin-mediated proteolysis. Genetic and biochemical evidence indicates that SUMO conjugation can ultimately lead to inactivation of sumoylated substrates by polysumoylation and/or ubiquitin-dependent degradation. Simultaneous inhibition of both mechanisms leads to severe phenotypic defects.


Received for publication, April 17, 2007 , and in revised form, August 21, 2007.

* This work was supported in part by National Institutes of Health Grant GM62268 (to E. S. J.), European Union Grant MERG-CT-2004-006344 (to G. J. K. P.), and Deutsche Forschungsgemeinschaft Grant SFB635 (to R. J. D.). 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.

Formula The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S5 and supplemental Tables S1 and S2.

1 Supported by a Deutsche Forschungsgemeinschaft Graduate Program "Genetics of Cellular Systems" predoctoral fellowship. Present address: Research Institute of Molecular Pathology, Dr. Bohrgasse 7, A-1030 Vienna, Austria.

2 Supported by a Center for Molecular Medicine Cologne predoctoral fellowship.

3 Supported by a North Rhine-Westphalia Graduate School "Functional Genetics and Genomics" predoctoral fellowship. Present address: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.

4 To whom correspondence should be addressed: Institute for Genetics, University of Cologne, Zülpicher Str. 47, D-50674 Cologne, Germany. Tel.: 49-221-470-4862; E-mail: j.dohmen{at}uni-koeln.de.


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


This article has been cited by other articles:


Home page
Mol. Biol. CellHome page
M. B. Kroetz, D. Su, and M. Hochstrasser
Essential Role of Nuclear Localization for Yeast Ulp2 SUMO Protease Function
Mol. Biol. Cell, April 15, 2009; 20(8): 2196 - 2206.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
Z. Wang and G. Prelich
Quality Control of a Transcriptional Regulator by SUMO-Targeted Degradation
Mol. Cell. Biol., April 1, 2009; 29(7): 1694 - 1706.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
J. Sollier, R. Driscoll, F. Castellucci, M. Foiani, S. P. Jackson, and D. Branzei
The Saccharomyces cerevisiae Esc2 and Smc5-6 Proteins Promote Sister Chromatid Junction-mediated Intra-S Repair
Mol. Biol. Cell, March 15, 2009; 20(6): 1671 - 1682.
[Abstract] [Full Text] [PDF]


Home page
Plant Physiol.Home page
R. Budhiraja, R. Hermkes, S. Muller, J. Schmidt, T. Colby, K. Panigrahi, G. Coupland, and A. Bachmair
Substrates Related to Chromatin and to RNA-Dependent Processes Are Modified by Arabidopsis SUMO Isoforms That Differ in a Conserved Residue with Influence on Desumoylation
Plant Physiology, March 1, 2009; 149(3): 1529 - 1540.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
L. Xiong, X. L. Chen, H. R. Silver, N. T. Ahmed, and E. S. Johnson
Deficient SUMO Attachment to Flp Recombinase Leads to Homologous Recombination-dependent Hyperamplification of the Yeast 2 {micro}m Circle Plasmid
Mol. Biol. Cell, February 1, 2009; 20(4): 1241 - 1251.
[Abstract] [Full Text] [PDF]


Home page
Arterioscler. Thromb. Vasc. Bio.Home page
K. Kawai-Kowase, T. Ohshima, H. Matsui, T. Tanaka, T. Shimizu, T. Iso, M. Arai, G. K. Owens, and M. Kurabayashi
PIAS1 Mediates TGF{beta}-Induced SM {alpha}-Actin Gene Expression Through Inhibition of KLF4 Function-Expression by Protein Sumoylation
Arterioscler. Thromb. Vasc. Biol., January 1, 2009; 29(1): 99 - 106.
[Abstract] [Full Text] [PDF]


Home page
GeneticsHome page
N. Meednu, H. Hoops, S. D'Silva, L. Pogorzala, S. Wood, D. Farkas, M. Sorrentino, E. Sia, P. Meluh, and R. K. Miller
The Spindle Positioning Protein Kar9p Interacts With the Sumoylation Machinery in Saccharomyces cerevisiae
Genetics, December 1, 2008; 180(4): 2033 - 2055.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
J. Lee, Y. Lee, M. J. Lee, E. Park, S. H. Kang, C. H. Chung, K. H. Lee, and K. Kim
Dual Modification of BMAL1 by SUMO2/3 and Ubiquitin Promotes Circadian Activation of the CLOCK/BMAL1 Complex
Mol. Cell. Biol., October 1, 2008; 28(19): 6056 - 6065.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
J. R. Mullen and S. J. Brill
Activation of the Slx5-Slx8 Ubiquitin Ligase by Poly-small Ubiquitin-like Modifier Conjugates
J. Biol. Chem., July 18, 2008; 283(29): 19912 - 19921.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
R. P. Darst, S. N. Garcia, M. R. Koch, and L. Pillus
Slx5 Promotes Transcriptional Silencing and Is Required for Robust Growth in the Absence of Sir2
Mol. Cell. Biol., February 15, 2008; 28(4): 1361 - 1372.
[Abstract] [Full Text] [PDF]


Home page
J. Biol. Chem.Home page
Y. Xie, O. Kerscher, M. B. Kroetz, H. F. McConchie, P. Sung, and M. Hochstrasser
The Yeast Hex3{middle dot}Slx8 Heterodimer Is a Ubiquitin Ligase Stimulated by Substrate Sumoylation
J. Biol. Chem., November 23, 2007; 282(47): 34176 - 34184.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2007 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement