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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}

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Cancer Res. 66, 6530-6539
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Viral Modulators of Cullin RING Ubiquitin Ligases: Culling the Host Defense.
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Mol. Cell. Biol. 26, 1235-1244
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J. Cell Sci. 119, 292-302
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Genetics 171, 1003-1015
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Cutting Edge: Bacterial Modulation of Epithelial Signaling via Changes in Neddylation of Cullin-1.
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CSN5/Jab1 Is Involved in Ligand-Dependent Degradation of Estrogen Receptor {alpha} by the Proteasome.
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The Jab1/COP9 signalosome subcomplex is a downstream mediator of Bcr-Abl kinase activity and facilitates cell-cycle progression.
K. Tomoda, J.-y. Kato, E. Tatsumi, T. Takahashi, Y. Matsuo, and N. Yoneda-Kato (2005)
Blood 105, 775-783
   Abstract »    Full Text »    PDF »
Translational Regulation via 5' mRNA Leader Sequences Revealed by Mutational Analysis of the Arabidopsis Translation Initiation Factor Subunit eIF3h.
T.-H. Kim, B.-H. Kim, A. Yahalom, D. A. Chamovitz, and A. G. von Arnim (2004)
PLANT CELL 16, 3341-3356
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The Arabidopsis CSN5A and CSN5B Subunits Are Present in Distinct COP9 Signalosome Complexes, and Mutations in Their JAMM Domains Exhibit Differential Dominant Negative Effects on Development.
G. Gusmaroli, S. Feng, and X. W. Deng (2004)
PLANT CELL 16, 2984-3001
   Abstract »    Full Text »    PDF »
Multiple Functions of Jab1 Are Required for Early Embryonic Development and Growth Potential in Mice.
K. Tomoda, N. Yoneda-Kato, A. Fukumoto, S. Yamanaka, and J.-y. Kato (2004)
J. Biol. Chem. 279, 43013-43018
   Abstract »    Full Text »    PDF »
Arabidopsis COP10 forms a complex with DDB1 and DET1 in vivo and enhances the activity of ubiquitin conjugating enzymes.
Y. Yanagawa, J. A. Sullivan, S. Komatsu, G. Gusmaroli, G. Suzuki, J. Yin, T. Ishibashi, Y. Saijo, V. Rubio, S. Kimura, et al. (2004)
Genes & Dev. 18, 2172-2181
   Abstract »    Full Text »    PDF »
Arabidopsis CAND1, an Unmodified CUL1-Interacting Protein, Is Involved in Multiple Developmental Pathways Controlled by Ubiquitin/Proteasome-Mediated Protein Degradation.
S. Feng, Y. Shen, J. A. Sullivan, V. Rubio, Y. Xiong, T.-p. Sun, and X. W. Deng (2004)
PLANT CELL 16, 1870-1882
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Arabidopsis ETA2, an Apparent Ortholog of the Human Cullin-Interacting Protein CAND1, Is Required for Auxin Responses Mediated by the SCFTIR1 Ubiquitin Ligase.
H.-w. Chuang, W. Zhang, and W. M. Gray (2004)
PLANT CELL 16, 1883-1897
   Abstract »    Full Text »    PDF »
Smad4 Protein Stability Is Regulated by Ubiquitin Ligase SCF{beta}-TrCP1.
M. Wan, Y. Tang, E. M. Tytler, C. Lu, B. Jin, S. M. Vickers, L. Yang, X. Shi, and X. Cao (2004)
J. Biol. Chem. 279, 14484-14487
   Abstract »    Full Text »    PDF »
Ddb1 Is Required for the Proteolysis of the Schizosaccharomyces pombe Replication Inhibitor Spd1 during S Phase and after DNA Damage.
T. Bondar, A. Ponomarev, and P. Raychaudhuri (2004)
J. Biol. Chem. 279, 9937-9943
   Abstract »    Full Text »    PDF »
Molecular Chaperone Hsp90 Associates with Resistance Protein N and Its Signaling Proteins SGT1 and Rar1 to Modulate an Innate Immune Response in Plants.
Y. Liu, T. Burch-Smith, M. Schiff, S. Feng, and S. P. Dinesh-Kumar (2004)
J. Biol. Chem. 279, 2101-2108
   Abstract »    Full Text »    PDF »
VACM-1, a cul-5 gene, inhibits cellular growth by a mechanism that involves MAPK and p53 signaling pathways.
C. Van Dort, P. Zhao, K. Parmelee, B. Capps, A. Poel, L. Listenberger, J. Kossoris, B. Wasilevich, D. Murrey, P. Clare, et al. (2003)
Am J Physiol Cell Physiol 285, C1386-C1396
   Abstract »    Full Text »    PDF »
Inositol 1,3,4-Trisphosphate 5/6-Kinase Inhibits Tumor Necrosis Factor-induced Apoptosis.
Y. Sun, Y. Mochizuki, and P. W. Majerus (2003)
J. Biol. Chem. 278, 43645-43653
   Abstract »    Full Text »    PDF »
Disruption of the COP9 Signalosome Csn2 Subunit in Mice Causes Deficient Cell Proliferation, Accumulation of p53 and Cyclin E, and Early Embryonic Death.
K. Lykke-Andersen, L. Schaefer, S. Menon, X.-W. Deng, J. B. Miller, and N. Wei (2003)
Mol. Cell. Biol. 23, 6790-6797
   Abstract »    Full Text »    PDF »
COP9 Signalosome Subunit 3 Is Essential for Maintenance of Cell Proliferation in the Mouse Embryonic Epiblast.
J. Yan, K. Walz, H. Nakamura, S. Carattini-Rivera, Q. Zhao, H. Vogel, N. Wei, M. J. Justice, A. Bradley, and J. R. Lupski (2003)
Mol. Cell. Biol. 23, 6798-6808
   Abstract »    Full Text »    PDF »

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