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Science 292 (5520): 1382-1385

Copyright © 2001 by the American Association for the Advancement of Science

Promotion of NEDD8-CUL1 Conjugate Cleavage by COP9 Signalosome

Svetlana Lyapina,1 Gregory Cope,1 Anna Shevchenko,3* Giovanna Serino,4 Tomohiko Tsuge,4 Chunshui Zhou,5 Dieter A. Wolf,5 Ning Wei,4 Andrej Shevchenko,3* Raymond J. Deshaies12dagger

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 the 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.

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

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

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   Abstract »    Full Text »    PDF »
The COP9 Signalosome Interacts Physically with SCFCOI1 and Modulates Jasmonate Responses.
S. Feng, L. Ma, X. Wang, D. Xie, S. P. Dinesh-Kumar, N. Wei, and X. W. Deng (2003)
PLANT CELL 15, 1083-1094
   Abstract »    Full Text »    PDF »
Skp1 and the F-box Protein Pof6 Are Essential for Cell Separation in Fission Yeast.
D. Hermand, S. Bamps, L. Tafforeau, J. Vandenhaute, and T. P. Makela (2003)
J. Biol. Chem. 278, 9671-9677
   Abstract »    Full Text »    PDF »
The NEDD8 Pathway Is Required for Proteasome-Mediated Degradation of Human Estrogen Receptor (ER)-{alpha} and Essential for the Antiproliferative Activity of ICI 182,780 in ER{alpha}-Positive Breast Cancer Cells.
M. Fan, R. M. Bigsby, and K. P. Nephew (2003)
Mol. Endocrinol. 17, 356-365
   Abstract »    Full Text »    PDF »
Characterization of the Last Subunit of the Arabidopsis COP9 Signalosome: Implications for the Overall Structure and Origin of the Complex.
G. Serino, H. Su, Z. Peng, T. Tsuge, N. Wei, H. Gu, and X. W. Deng (2003)
PLANT CELL 15, 719-731
   Abstract »    Full Text »    PDF »
Plasma Membrane H+-ATPase Is Involved in Auxin-Mediated Cell Elongation during Wheat Embryo Development.
N. Rober-Kleber, J. T.P. Albrechtova, S. Fleig, N. Huck, W. Michalke, E. Wagner, V. Speth, G. Neuhaus, and C. Fischer-Iglesias (2003)
Plant Physiology 131, 1302-1312
   Abstract »    Full Text »    PDF »
Enforced expression of CUL-4A interferes with granulocytic differentiation and exit from the cell cycle.
B. Li, F.-C. Yang, D. W. Clapp, and K. T. Chun (2003)
Blood 101, 1769-1776
   Abstract »    Full Text »    PDF »
Arabidopsis E2Fc Functions in Cell Division and Is Degraded by the Ubiquitin-SCFAtSKP2 Pathway in Response to Light.
J. C. del Pozo, M. B. Boniotti, and C. Gutierrez (2002)
PLANT CELL 14, 3057-3071
   Abstract »    Full Text »    PDF »
Inositol 1,3,4-Trisphosphate 5/6-Kinase Associates with the COP9 Signalosome by Binding to CSN1.
Y. Sun, M. P. Wilson, and P. W. Majerus (2002)
J. Biol. Chem. 277, 45759-45764
   Abstract »    Full Text »    PDF »
MOLECULAR BIOLOGY: New Proteases in a Ubiquitin Stew.
M. Hochstrasser (2002)
Science 298, 549-552
   Abstract »    Full Text »    PDF »
Role of Rpn11 Metalloprotease in Deubiquitination and Degradation by the 26S Proteasome.
R. Verma, L. Aravind, R. Oania, W. H. McDonald, J. R. Yates III, E. V. Koonin, and R. J. Deshaies (2002)
Science 298, 611-615
   Abstract »    Full Text »    PDF »
Role of Predicted Metalloprotease Motif of Jab1/Csn5 in Cleavage of Nedd8 from Cul1.
G. A. Cope, G. S. B. Suh, L. Aravind, S. E. Schwarz, S. L. Zipursky, E. V. Koonin, and R. J. Deshaies (2002)
Science 298, 608-611
   Abstract »    Full Text »    PDF »
Multiple Ubiquitin Ligase-Mediated Processes Require COP9 Signalosome and AXR1 Function.
C. Schwechheimer, G. Serino, and X.-W. Deng (2002)
PLANT CELL 14, 2553-2563
   Abstract »    Full Text »    PDF »
Dysregulation of protein modification by ISG15 results in brain cell injury.
K. J. Ritchie, M. P. Malakhov, C. J. Hetherington, L. Zhou, M.-T. Little, O. A. Malakhova, J. C. Sipe, S. H. Orkin, and D.-E. Zhang (2002)
Genes & Dev. 16, 2207-2212
   Abstract »    Full Text »    PDF »
Role of the Arabidopsis RING-H2 Protein RBX1 in RUB Modification and SCF Function.
W. M. Gray, H. Hellmann, S. Dharmasiri, and M. Estelle (2002)
PLANT CELL 14, 2137-2144
   Abstract »    Full Text »    PDF »
The SCFCOI1 Ubiquitin-Ligase Complexes Are Required for Jasmonate Response in Arabidopsis.
L. Xu, F. Liu, E. Lechner, P. Genschik, W. L. Crosby, H. Ma, W. Peng, D. Huang, and D. Xie (2002)
PLANT CELL 14, 1919-1935
   Abstract »    Full Text »    PDF »
Role of SCF Ubiquitin-Ligase and the COP9 Signalosome in the N Gene-Mediated Resistance Response to Tobacco mosaic virus.
Y. Liu, M. Schiff, G. Serino, X.-W. Deng, and S. P. Dinesh-Kumar (2002)
PLANT CELL 14, 1483-1496
   Abstract »    Full Text »    PDF »
The NEDD8 Pathway Is Essential for SCFbeta -TrCP-mediated Ubiquitination and Processing of the NF-kappa B Precursor p105.
R. E. Amir, K. Iwai, and A. Ciechanover (2002)
J. Biol. Chem. 277, 23253-23259
   Abstract »    Full Text »    PDF »

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