Abstract
Ubiquitin carboxyl-terminal hydrolase 37 (UCH37, also called UCHL5), a member of the deubiquitinating enzymes, can suppress protein degradation through disassembling polyubiquitin from the distal subunit of the chain. It has been proved that UCH37 can be activated by proteasome ubiqutin chain receptor Rpn13 and incorporation into the 19S complex. UCH37, which has been reported to assist in the mental development of mice, may play an important role in oncogenesis, tumor invasion and migration. Further studies will allow a better understanding of roles in cell physiology and pathology, embryonic development and tumor formation, hopefully providing support for the idea that UCH37 may constitute a new interesting target for the development of anticancer drugs.
Highlights
Fang et al, 2010; Lee et al, 2011; Fang et al, 2013).The ubiquitin-26S proteasome system is the main nonlysosomal route for intracellular protein degradation in eukaryotes
It has been proved that UCH37 can be activated by proteasome ubiqutin chain receptor Rpn13 and incorporation into the 19S complex
UCH37, which has been reported to assist in the mental development of mice, may play an important role in oncogenesis, tumor invasion and migration
Summary
Fang et al, 2010; Lee et al, 2011; Fang et al, 2013). The ubiquitin-26S proteasome system is the main nonlysosomal route for intracellular protein degradation in eukaryotes. A new study on the structure of C-terminal extension of UCH37 by Burgie SE et al found that the crystallographic tetramer of UCH37 predicted its autoinhibition, as Helix 9 would occlude the ubiquitin binding-site. Whether it is degraded by lysosomal route or ubiquitin-26S proteasome system needs further investigation Several studies, performed both in vivo and in vitro, have suggested that UCH37 can suppress protein degradation through disassembles polyubiquitin from the distal subunit of the chain, shortening it such that poorly ubiquitinated substrates can be rescued from being degraded (Lam et al, 1997b; Husnjak et al, 2008; Koulich et al, 2008; Schreiner et al, 2008; Jacobson et al, 2009). Over-expression of UCH37 leads to the opposite effect (Chen et al, 2011)
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