Isopeptidase

The last two enzymatic activities that we have described in reticulocytes are ubiquitin C-terminal isopeptidases, which act at the final stages of the ubiquitin proteo-... 

The study of DUBs has moved at a rapid rate since their initial discovery in the early 1980s. Yet despite all the progress, the total number of DUBs and the substrate specificity of most DUBs are still undetermined. The discovery of novel DUB families including the JAMM isopeptidases and OTU DUBs has highlighted that there may be still more unidentified DUBs. Because of the large number of... 

VDUl human JAMM Isopeptidases unknown regulation of Ub-proteasome pathway [64]... 

Gong, L., Kamitani, T., Millas, S., and Yeh, E. T. Identification of a novel isopeptidase with dual specificity for ubiquitin- and NEDD8-conjugated proteins, J Biol Chem, 2000, 275, 14212-6. 

Li, S. j. and Hochstrasser, M. The Ulpl SUMO isopeptidase distinct domains required for viability, nuclear envelope localization, and substrate specificity, J Cdl Biol, 2003, 160, 1069— 81. 

R. Deubiquitination step in the endocytic pathway of yeast plasma membrane proteins crucial role of Doa4p ubiquitin isopeptidase, Mol Cell Biol, 2001, 21, 4482-94. 

G. F. UBPY a growth-regulated human ubiquitin isopeptidase, Embo J, 1998, 17, 3241-50. 

LLadari, T., Warms, J. V., Rose, I. A., and Hershko, A. A ubiquitin C-terminal isopeptidase that acts on polyubiquitin chains. Role in protein degradation, J Biol Chem, 1992, 267, 719-27. 

Pickart, C. M., and Cohen, R. E. Specificity of the ubiquitin isopeptidase in the PA700 regulatory complex of 26S proteasomes. J. Biol. Chem. 1997, 272, 28483-28446. 

Melchior, F., Schergaut, M., and Pichler, a., SUMO ligases, isopeptidases and nuclear pores. 

Figure 11 The SUMO conjugation pathway. SUMO (open drop-shaped objects) is synthesized with a C-terminai extension. SUMO-specific isopeptidases (SENPs) cieave the C-terminai extension from the SUMO precursor to produce a mature protein with giycine at the C-terminai. The mature SUMO is activated by an E1 heterodimerconsistingof Uba2 and AOS1 in an ATP-dependent reaction. The action of E1 produces a SUMO-AMP intermediate (fiiied drop-shaped object), which is passed onto an E2 caiied Ubc9. E2 passes SUMO onto an E3 iigase, which attaches SUMO to the substrate. SUMO attachment is reversibie and can be removed by SENPs.

SUMO attachment can be removed by SUMO-specific isopeptidases just as UCHs and UBPs remove ubiquitin from substrate proteins. Thus, sumoylation is also a reversible modification. SUMO-specific isopeptidases possess a Cys residue in their catalytic core similar to UCHs and UBPs. Two SUMO-specific isopeptidases in yeast are called Ulpl and Ulp2. In humans, six Ulp homologues have been identified and are given the name sentrin-specific proteases (SENPs) because SUMO was previously known as sentrin . 

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