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Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

The SCF-type E3 Ubiquitin Ligases as Cancer Targets

Author(s): Kyoko Kitagawa and Masatoshi Kitagawa

Volume 16, Issue 2, 2016

Page: [119 - 129] Pages: 11

DOI: 10.2174/1568009616666151112122231

Price: $65

Abstract

The ubiquitin system controls protein stability and function. F-box proteins form SCF (SKP1-Cullin1-F-box protein)-type ubiquitin (E3) ligases to selectively target their substrates for degradation via the ubiquitin–proteasome pathway. Here, we review F-box proteins associated with cancer development. S-phase kinase-associated protein 2 (SKP2) (also known as FBXL1) is often overexpressed in human cancers, and functions as an oncogenic E3 ligase to degrade tumor suppressor gene products. Moreover, F-box/WD repeat-containing protein 7 (FBXW7) (also known as Fbw7) is often mutated in human cancers and functions as a tumor suppressive E3 ligase targeting oncogenic proteins for degradation. SKP2 is a potential drug target for cancer therapy and FBXW7 is useful in determining patient diagnosis, prognosis, and drug sensitivity. In this review, we also discuss other F-box proteins involved in cancer-associated cellular processes such as cell cycle control, epigenetic regulation, epithelial mesenchymal transition, apoptosis/survival, drug resistance, and DNA-damage responses.

Keywords: β-TrCP, E3 ligase, F-box protein, FBXW7, human cancer, proteasome, SCF complex, SKP2, ubiquitin.


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