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Role of Predicted Metalloprotease Motif of Jab1/Csn5 in Cleavage of Nedd8 from Cul1

Cope, Gregory A. and Suh, Greg S. and Aravind, L. and Schwarz, Sylvia E. and Zipursky, S. Lawrence and Koonin, Eugene V. and Deshaies, Raymond J. (2002) Role of Predicted Metalloprotease Motif of Jab1/Csn5 in Cleavage of Nedd8 from Cul1. Science, 298 (5593). pp. 608-611. ISSN 0036-8075. doi:10.1126/science.1075901.

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COP9 signalosome (CSN) cleaves the ubiquitin-like protein Nedd8 from the Cul1 subunit of SCF ubiquitin ligases. The Jab1/MPN domain metalloenzyme (JAMM) motif in the Jab1/Csn5 subunit was found to underlie CSN's Nedd8 isopeptidase activity. JAMM is found in proteins from archaea, bacteria, and eukaryotes, including the Rpn11 subunit of the 26S proteasome. Metal chelators and point mutations within JAMM abolished CSN-dependent cleavage of Nedd8 from Cul1, yet had little effect on CSN complex assembly. Optimal SCF activity in yeast and both viability and proper photoreceptor cell (R cell) development in Drosophila melanogaster required an intact Csn5 JAMM domain. We propose that JAMM isopeptidases play important roles in a variety of physiological pathways.

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Deshaies, Raymond J.0000-0002-3671-9354
Additional Information:© 2002 American Association for the Advancement of Science. 9 July 2002; accepted 7 August 2002. Published online 15 August 2002; 10.1126/science.1075901. Include this information when citing this paper. We thank D. Wolf, M. Hochstrasser, K. Mundt, and A. Carr for generously providing yeast strains and plasmids, the S. Benzer lab for providing lab equipment and space, and S. Lyapina for psCSN. We thank members of the Deshaies lab for providing helpful insight and discussions. This work was supported by NIH (G.A.C.) and the Howard Hughes Medical Institute.
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Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:5593
Record Number:CaltechAUTHORS:20141118-152419645
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Official Citation:Role of Predicted Metalloprotease Motif of Jab1/Csn5 in Cleavage of Nedd8 from Cul1 Gregory A. Cope, Greg S. B. Suh, L. Aravind, Sylvia E. Schwarz, S. Lawrence Zipursky, Eugene V. Koonin, and Raymond J. Deshaies Science 18 October 2002: 298 (5593), 608-611.Published online 15 August 2002 [DOI:10.1126/science.1075901]
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:51926
Deposited By: Ruth Sustaita
Deposited On:18 Nov 2014 23:56
Last Modified:10 Nov 2021 19:17

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