TY - JOUR
T1 - The ubiquitin pathway
T2 - An emerging drug target in cancer therapy
AU - Ande, Sudharsana Rao
AU - Chen, Junjie
AU - Maddika, Subbareddy
N1 - Funding Information:
S.R.A is a recipient of MHRC Postdoctoral Fellowship, Winnipeg. This work was supported in part by grants from the National Institutes of Health (to J.C). J.C is a recipient of an Era of Hope Scholars award from Department of Defense and a member of Mayo Clinic Breast SPORE program.
PY - 2009/12/25
Y1 - 2009/12/25
N2 - 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.
AB - 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.
KW - Cancer therapy
KW - Deubiquitinases
KW - E3 ligase
KW - Inhibitors
KW - Proteosome
KW - Ubiquitin
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U2 - 10.1016/j.ejphar.2009.08.042
DO - 10.1016/j.ejphar.2009.08.042
M3 - Review article
C2 - 19835866
AN - SCOPUS:71749086813
SN - 0014-2999
VL - 625
SP - 199
EP - 205
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -