By Angelika M. Burger, Arun K. Seth (auth.), Eric Rubin, Kathleen Sakamoto (eds.)

This booklet comprises chapters written by way of specialists within the box of the ubiquitin proteasome process and melanoma. The authors have summarized present info on ubiquitin ligases and proteasomes as power goals for melanoma remedy. issues lined within the ebook contain an outline of ubiquitin ligases, deubiquitinating enzymes, and the proteasome. particular ailments caused by deregulated ubiquitin ligases, corresponding to Von-Hippel-Lindau sickness and Fanconi anemia also are mentioned. eventually, novel ways and medication to focus on proteins fascinated by sumoylation, ubiquitination, and degradation are described.

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Thus continued research into other possible sites of proteasomal intervention would be deemed prudent (Fig. 1), and these are described below. (a) Targeting the Receptor Pathway. (b) Targeting the JAMM domain-containing deubiquitinating enzyme (DUB) RPN11/POH1/S13 and other proteasomal DUBs. (c) Targeting the ATPases. (d) Targeting the ATPase-20S core interface. Lid Recruitment: Ubistatins Isopeptidase: ? 19S RP Base Unfoldase: RIP-1 α Gating; PR39 β 20S CP β Peptidase: Bortezomib, Lactacystin α Fig.

Similarly, given the prevalence of REGg in brain tissue, it may prove fruitful to identify inhibitors of the REGg-CP pathway and test them against neurological tumors. It is hoped that such studies will enhance our basic understanding of the proteasome, and at the same time lead to the development of anti-cancer drugs that prolong life without significantly affecting its quality. References Adams, J. (2004). The proteasome: a suitable antineoplastic target. Nat Rev Cancer 4, 349–360. L. (1998).

Biochem Biophys Res Commun 364, 226–230. , and Finley, D. (2005). Delivery of ubiquitinated substrates to protein-unfolding machines. Nat Cell Biol 7, 742–749. , and Simons, M. (2003). Proline- and arginine-rich peptides constitute a novel class of allosteric inhibitors of proteasome activity. Biochemistry 42, 8663–8670. J. (2007). The JAMM motif of human deubiquitinase Poh1 is essential for cell viability. Mol Cancer Ther 6, 262–268. , et al. (2000). Inhibition of ubiquitin-proteasome pathway-mediated I kappa B alpha degradation by a naturally occurring antibacterial peptide.

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