E3 ubiquitin ligases as cancer targets and biomarkers.
E3 ubiquitin ligases are a large family of proteins that are engaged in the regulation of the turnover and activity of many target proteins. Together with ubiquitin-activating enzyme E1 and ubiquitin-conjugating enzyme E2, E3 ubiquitin ligases catalyze the ubiquitination of a variety of biologically significant protein substrates for targeted degradation through the 26S proteasome, as well as for nonproteolytic regulation of their functions or subcellular localizations. E3 ubiquitin ligases, therefore, play an essential role in the regulation of many biologic processes. Increasing amounts of evidence strongly suggest that the abnormal regulation of some E3 ligases is involved in cancer development. Furthermore, some E3 ubiquitin ligases are frequently overexpressed in human cancers, which correlates well with increased chemoresistance and poor clinic prognosis. In this review, E3 ubiquitin ligases (such as murine double minute 2, inhibitor of apoptosis protein, and Skp1-Cullin-F-box protein) will be evaluated as potential cancer drug targets and prognostic biomarkers. Extensive study in this field would lead to a better understanding of the molecular mechanism by which E3 ligases regulate cellular processes and of how their deregulations contribute to carcinogenesis. This would eventually lead to the development of a novel class of anticancer drugs targeting specific E3 ubiquitin ligases, as well as the development of sensitive biomarkers for cancer treatment, diagnosis, and prognosis.
Sun
Yi
Y
Division of Cancer Biology, Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109-0936, USA. sunyi@umich.edu
D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002471:Cell Transformation, Neoplastic; D005786:Gene Expression Regulation; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000503:physiopathology; D011506:Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000032:analysis* / Q000378:metabolism*
D014408:Biomarkers, Tumor; D011506:Proteins; D044767:Ubiquitin-Protein Ligases