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Originally published in Science Express on 15 August 2002
Science 18 October 2002:
Vol. 298. no. 5593, pp. 608 - 611
DOI: 10.1126/science.1075901
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Reports

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

Gregory A. Cope,1 Greg S. B. Suh,3* L. Aravind,4 Sylvia E. Schwarz,1dagger S. Lawrence Zipursky,23 Eugene V. Koonin,4 Raymond J. Deshaies12ddagger

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.

1 Department of Biology, California Institute of Technology (CalTech), Pasadena, CA 91125, USA.
2 Howard Hughes Medical Institute,
3 Department of Biological Chemistry, The School of Medicine, University of California at Los Angeles (UCLA), Los Angeles, CA 90095, USA.
4 National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
*   Present address: Department of Biology, California Institute of Technology, Pasadena, CA 91125, USA.

dagger    Present address: G2M Cancer Drugs AG, Frankfurt/Main, Germany.

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

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