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Published Online May 3, 2001
Science DOI: 10.1126/science.1059780

Reports

Submitted on February 12, 2001
Accepted on April 17, 2001

Promotion of NEDD8-CUL1 Conjugate Cleavage by COP9 Signalosome

Svetlana Lyapina 1, Gregory Cope 1, Anna Shevchenko 2, Giovanna Serino 3, Tomohiko Tsuge 3, Chunshui Zhou 4, Dieter A. Wolf 4, Ning Wei 3, Andrej Shevchenko 2, Raymond J. Deshaies 5*

1 Department of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
2 Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany; Protein and Peptide Group, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69012 Heidelberg, Germany.
3 Department of Molecular, Cellular and Developmental Biology, Yale University, Post Office Box 208104, New Haven, CT 06520, USA.
4 Department of Cancer Cell Biology, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
5 Department of Biology, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.

* To whom correspondence should be addressed. E-mail: deshaies{at}caltech.edu.

SCF ubiquitin ligases control various processes by marking regulatory proteins for ubiquitin-dependent proteolysis. To illuminate how SCF complexes are regulated, we sought proteins that interact with human SCF component CUL1. The COP9/Signalosome (CSN), a suppressor of plant photomorphogenesis, associated with multiple cullins and promoted cleavage of the ubiquitin-like protein NEDD8 from Schizosaccharomyces pombe CUL1 in vivo and in vitro. Multiple NEDD8-modified proteins uniquely accumulated in CSN-deficient S. pombe cells. We propose that the broad spectrum of activities previously attributed to CSN subunits, including repression of photomorphogenesis, activation of JUN, and activation of p27 nuclear export, underscores the importance of dynamic cycles of NEDD8 attachment and removal in biological regulation.


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Ubiquitination and Auxin Signaling: A Degrading Story.
S. Kepinski and O. Leyser (2002)
PLANT CELL 14, S81-95
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The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction.
M. H. Glickman and A. Ciechanover (2002)
Physiol Rev 82, 373-428
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Role of a Ubiquitin-Like Modification in Polarized Morphogenesis.
G. A. G. Dittmar, C. R. M. Wilkinson, P. T. Jedrzejewski, and D. Finley (2002)
Science 295, 2442-2446
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The RAR1 Interactor SGT1, an Essential Component of R Gene-Triggered Disease Resistance.
C. Azevedo, A. Sadanandom, K. Kitagawa, A. Freialdenhoven, K. Shirasu, and P. Schulze-Lefert (2002)
Science 295, 2073-2076
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Regulatory Role of SGT1 in Early R Gene-Mediated Plant Defenses.
M. J. Austin, P. Muskett, K. Kahn, B. J. Feys, J. D. G. Jones, and J. E. Parker (2002)
Science 295, 2077-2080
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Arabidopsis COP10 is a ubiquitin-conjugating enzyme variant that acts together with COP1 and the COP9 signalosome in repressing photomorphogenesis.
G. Suzuki, Y. Yanagawa, S. F. Kwok, M. Matsui, and X.-W. Deng (2002)
Genes & Dev. 16, 554-559
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The Activating Enzyme of NEDD8 Inhibits Steroid Receptor Function.
M. Fan, X. Long, J. A. Bailey, C. A. Reed, E. Osborne, E. A. Gize, E. A. Kirk, R. M. Bigsby, and K. P. Nephew (2002)
Mol. Endocrinol. 16, 315-330
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CSN5/Jab1 mutations affect axis formation in the Drosophila oocyte by activating a meiotic checkpoint.
S. Doronkin, I. Djagaeva, and S. K. Beckendorf (2002)
Development 129, 5053-5064
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The Nedd8-conjugated ROC1-CUL1 Core Ubiquitin Ligase Utilizes Nedd8 Charged Surface Residues for Efficient Polyubiquitin Chain Assembly Catalyzed by Cdc34.
K. Wu, A. Chen, P. Tan, and Z.-Q. Pan (2002)
J. Biol. Chem. 277, 516-527
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The COP9 signalosome: at the interface between signal transduction and ubiquitin-dependent proteolysis.
D. Bech-Otschir, M. Seeger, and W. Dubiel (2002)
J. Cell Sci. 115, 467-473
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Charting the Protein Complexome in Yeast by Mass Spectrometry.
R. J. Deshaies, J. H. Seol, W. H. McDonald, G. Cope, S. Lyapina, A. Shevchenko, A. Shevchenko, R. Verma, and J. R. Yates III (2002)
Mol. Cell. Proteomics 1, 3-10
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Targeting of NEDD8 and Its Conjugates for Proteasomal Degradation by NUB1.
T. Kamitani, K. Kito, T. Fukuda-Kamitani, and E. T. H. Yeh (2001)
J. Biol. Chem. 276, 46655-46660
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Molecular Characterization of Subunit 6 of the COP9 Signalosome and Its Role in Multifaceted Developmental Processes in Arabidopsis.
Z. Peng, G. Serino, and X.-W. Deng (2001)
PLANT CELL 13, 2393-2407
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Interactions of the COP9 Signalosome with the E3 Ubiquitin Ligase SCFTIR1 in Mediating Auxin Response.
C. Schwechheimer, G. Serino, J. Callis, W. L. Crosby, S. Lyapina, R. J. Deshaies, W. M. Gray, M. Estelle, and X.-W. Deng (2001)
Science 292, 1379-1382
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Saccharomyces cerevisiae Protein Pci8p and Human Protein eIF3e/Int-6 Interact with the eIF3 Core Complex by Binding to Cognate eIF3b Subunits.
A. Shalev, L. Valasek, C. A. Pise-Masison, M. Radonovich, L. Phan, J. Clayton, H. He, J. N. Brady, A. G. Hinnebusch, and K. Asano (2001)
J. Biol. Chem. 276, 34948-34957
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The Cytoplasmic Shuttling and Subsequent Degradation of p27Kip1 Mediated by Jab1/CSN5 and the COP9 Signalosome Complex.
K. Tomoda, Y. Kubota, Y. Arata, S. Mori, M. Maeda, T. Tanaka, M. Yoshida, N. Yoneda-Kato, and J.-y. Kato (2002)
J. Biol. Chem. 277, 2302-2310
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Inositol 1,3,4-Trisphosphate 5/6-Kinase Is a Protein Kinase That Phosphorylates the Transcription Factors c-Jun and ATF-2.
M. P. Wilson, Y. Sun, L. Cao, and P. W. Majerus (2001)
J. Biol. Chem. 276, 40998-41004
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