The ubiquitin pathway: an emerging drug target in cancer therapy.
Ubiquitination is a highly ordered multistep enzymatic process, carried out by a well-defined systematic ubiquitin pathway, which is required for maintaining appropriate levels and functional activities of various cellular proteins. Targeted regulation of proteins by ubiquitin pathway controls numerous cellular processes including cell proliferation, signal transduction, apoptosis, transcriptional regulation, receptor modulation as well as endocytosis. Significant progress has been made in recent years in not only understanding the structure, function and important regulatory roles of ubiquitin network but also the alterations of ubiquitin pathway in various human diseases including cancer. Based on the progress made, it is now possible to target specifically various components involved in the ubiquitin pathway such as E3 ubiquitin ligases, deubiquitinases and proteosome for potential anticancer therapies. Here we review the potential drug targets available in the ubiquitin system and the small molecule inhibitors that can target these components in the pathway, which can be developed into novel anticancer therapeutics in the near future.
Ande
Sudharsana Rao
SR
Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Chen
Junjie
J
Maddika
Subbareddy
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases / Q000187:drug effects* / Q000378:metabolism; D054875:Ubiquitination / Q000187:drug effects
D000970:Antineoplastic Agents; D044767:Ubiquitin-Protein Ligases