Recent advances in SCF ubiquitin ligase complex: Clinical implications

Abstract

F-box proteins, which are subunit recruiting modules of SCF (SKP1-Cullin 1-F-box protein) E3 ligase complexes, play critical roles in the development and progression of human malignancies through governing multiple cellular processes including cell proliferation, apoptosis, invasion and metastasis. Moreover, there are emerging studies that lead to the development of F-box proteins inhibitors with promising therapeutic potential. In this article, we describe how F-box proteins including but not restricted to well-established Fbw7, Skp2 and β-TRCP, are involved in tumorigenesis. However, in-depth investigation is required to further explore the mechanism and the physiological contribution of undetermined F-box proteins in carcinogenesis. Lastly, we suggest that targeting F-box proteins could possibly open new avenues for the treatment and prevention of human cancers.

Keywords: F-box protein; Human cancer; Oncoprotein; Tumor suppressor; Ubiquitin.

Figure 1

A schematic illustration of the E1-E2-E3 cascade-mediated ubiquitin transfer process.

Figure 2

A schematic illustration of structural organization of the multiple-subunit SCF E3 ubiquitin ligase complexes.