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Science 298 (5593): 549-552

Copyright © 2002 by the American Association for the Advancement of Science

New Proteases in a Ubiquitin Stew

Mark Hochstrasser

Proteins destined for degradation in the cell's garbage disposal unit, the proteasome, must first receive a ubiquitin tag. In his Perspective, Hochstrasser discusses new work (Verma et al., Cope et al.) that reveals the vital link between removal of the ubiquitin tag in the proteasome and degradation of the targeted protein. Proteins are deubiquitinated in the proteasome by a zinc-dependent metalloprotease, and protein degradation cannot take place in the absence of this enzyme.

The author is in the Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA. E-mail: mark.hochstrasser{at}

K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated Brcc36 and proteasomal Poh1.
E. M. Cooper, C. Cutcliffe, T. Z. Kristiansen, A. Pandey, C. M. Pickart, and R. E. Cohen (2009)
EMBO J. 28, 621-631
   Abstract »    Full Text »    PDF »
Dissection of the Carboxyl-Terminal Domain of the Proteasomal Subunit Rpn11 in Maintenance of Mitochondrial Structure and Function.
T. Rinaldi, L. Hofmann, A. Gambadoro, R. Cossard, N. Livnat-Levanon, M. H. Glickman, L. Frontali, and A. Delahodde (2008)
Mol. Biol. Cell 19, 1022-1031
   Abstract »    Full Text »    PDF »
Ubiquitin proteasome pathway gene expression varies in rhesus monkey oocytes and embryos of different developmental potential.
N. R. Mtango and K. E. Latham (2007)
Physiol Genomics 31, 1-14
   Abstract »    Full Text »    PDF »
The JAMM motif of human deubiquitinase Poh1 is essential for cell viability.
M. Gallery, J. L. Blank, Y. Lin, J. A. Gutierrez, J. C. Pulido, D. Rappoli, S. Badola, M. Rolfe, and K. J. MacBeth (2007)
Mol. Cancer Ther. 6, 262-268
   Abstract »    Full Text »    PDF »
Sem1, the yeast ortholog of a human BRCA2-binding protein, is a component of the proteasome regulatory particle that enhances proteasome stability.
M. Funakoshi, X. Li, I. Velichutina, M. Hochstrasser, and H. Kobayashi (2004)
J. Cell Sci. 117, 6447-6454
   Abstract »    Full Text »    PDF »
Proteasomal Interference Prevents Zona Pellucida Penetration and Fertilization in Mammals.
P. Sutovsky, G. Manandhar, T. C. McCauley, J. N. Caamano, M. Sutovsky, W. E. Thompson, and B. N. Day (2004)
Biol Reprod 71, 1625-1637
   Abstract »    Full Text »    PDF »
AMSH is an endosome-associated ubiquitin isopeptidase.
J. McCullough, M. J. Clague, and S. Urbe (2004)
J. Cell Biol. 166, 487-492
   Abstract »    Full Text »    PDF »
Ubiquitination of {alpha}-Synuclein in Lewy Bodies Is a Pathological Event Not Associated with Impairment of Proteasome Function.
G. K. Tofaris, A. Razzaq, B. Ghetti, K. S. Lilley, and M. G. Spillantini (2003)
J. Biol. Chem. 278, 44405-44411
   Abstract »    Full Text »    PDF »
NEDP1, a Highly Conserved Cysteine Protease That deNEDDylates Cullins.
H. M. Mendoza, L.-n. Shen, C. Botting, A. Lewis, J. Chen, B. Ink, and R. T. Hay (2003)
J. Biol. Chem. 278, 25637-25643
   Abstract »    Full Text »    PDF »
Exploring the repertoire of RNA secondary motifs using graph theory; implications for RNA design.
H. H. Gan, S. Pasquali, and T. Schlick (2003)
Nucleic Acids Res. 31, 2926-2943
   Abstract »    Full Text »    PDF »

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