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A new protease required for cell-cycle progression in yeast

Nature volume 398, pages 246–251 (1999)Cite this article

Abstract

In eukaryotes, protein function can be modulated by ligation to ubiquitin or to ubiquitin-like proteins (Ubl proteins)1,2,3. The vertebrate Ubl protein SUMO-1 is only 18% identical to ubiquitin but is 48% identical to the yeast protein Smt3. Both SUMO-1 and Smt3 are ligated to cellular proteins, and protein conjugation to SUMO-1/Smt3 is involved in many physiological processes3,4,5,6,7,8,9,10. It remained unknown, however, whether deconjugation of SUMO-1/Smt3 from proteins is also essential. Here we describe a yeast Ubl-specific protease, Ulp1, which cleaves proteins from Smt3 and SUMO-1 but not from ubiquitin. Ulp1 is unrelated to any known deubiquitinating enzyme but shows distant similarity to certain viral proteases, indicating the existence of a widely conserved protease fold. Proteins related to Ulp1 are present in many organisms, including several human pathogens. The pattern of Smt3-coupled proteins in yeast changes markedly throughout the cell cycle, and specific conjugates accumulate in ulp1 mutants. Ulp1 has several functions, including an essential role in the G2/M phase of the cell cycle.

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Figure 1: Characterization of the Ulp1 enzyme.
Figure 2: Ulp1 is a new type of cysteine protease.
Figure 3: Mutagenesis of putative Ulp1 active-site residues and characterization of ulp1 mutants.
Figure 4: Ulp1 is required for cell-cycle progression.
Figure 5: Smt3–protein conjugates in yeast.

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Acknowledgements

We thank M. Matunis for the RanGAP1 cDNA expression constructs; R. Swanson for help with immunofluorescence microscopy; R. Cohen for ubiquitin aldehyde; J. Choy for help with FACS analysis; B. Lieberman for plasmids; the University of Chicago Oligopeptide Synthesis facility for N-terminal protein sequencing; and A. Amerik, J. Laney, S. Swaminathan, R. Swanson and A. Turkewitz for critical reading of the manuscript. This work was supported by a grant from the NIH.

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  1. Department of Biochemistry & Molecular Biology, University of Chicago, 920 East 58th Street, Chicago, 60637, Illinois, USA

    Shyr-Jiann Li & Mark Hochstrasser

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Correspondence to Mark Hochstrasser.

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Li, SJ., Hochstrasser, M. A new protease required for cell-cycle progression in yeast. Nature 398, 246–251 (1999). https://doi.org/10.1038/18457

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