Molecular targeting of E3 ligases--a therapeutic approach for cancer.
BACKGROUND
The ubiquitin-proteasomal degradation pathway plays a critical role in protein degradation and regulates a wide variety of cellular functions. This highly conserved post-translational modification of proteolytic processes is mainly carried out by substrate-specific E3 ligases. The deregulation of E3 ligases contributes to cancer development and their overexpression is often associated with poor prognosis.


OBJECTIVE
We review the current understanding of E3 ligases, their functional role in cancer pathogenesis, current progress and development of certain ubiquitin E3 ligases as targets for therapeutic intervention.


METHODS
Preclinical and clinical data for E3 ligase inhibitors available in the public domain are discussed.


CONCLUSIONS
With the growing understanding of their role in cancer development and progression, E3 ligases have emerged as potential anticancer targets for therapeutic intervention.
Lakshmanan
Manikandan
M
Ranbaxy Laboratories Ltd, New Drug Discovery Research, R&D-III, Sector-18, Plot No. 20, Gurgaon-122015, India.
Bughani
Usha
U
Duraisamy
Senthil
S
Diwan
Manish
M
Dastidar
Sunanda
S
Ray
Abhijit
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D011379:Prognosis; D011499:Protein Processing, Post-Translational / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000187:drug effects* / Q000378:metabolism
D000970:Antineoplastic Agents; D044767:Ubiquitin-Protein Ligases