Recent insight into the role of FBXW7 as a tumor suppressor

Kanae Yumimoto; Keiichi I Nakayama

doi:10.1016/j.semcancer.2020.02.017

Recent insight into the role of FBXW7 as a tumor suppressor

Semin Cancer Biol. 2020 Dec;67(Pt 2):1-15. doi: 10.1016/j.semcancer.2020.02.017. Epub 2020 Feb 27.

Authors

Kanae Yumimoto¹, Keiichi I Nakayama²

Affiliations

¹ Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka, 812-8582, Japan.
² Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka, 812-8582, Japan. Electronic address: nakayak1@bioreg.kyushu-u.ac.jp.

PMID: 32113998
DOI: 10.1016/j.semcancer.2020.02.017

Abstract

FBXW7 (also known as Fbw7, Sel10, hCDC4, or hAgo) is a tumor suppressor and the most frequently mutated member of the F-box protein family in human cancers. FBXW7 functions as the substrate recognition component of an SCF-type E3 ubiquitin ligase. It specifically controls the proteasome-mediated degradation of many oncoproteins such as c-MYC, NOTCH, KLF5, cyclin E, c-JUN, and MCL1. In this review, we summarize the molecular and biological features of FBXW7 and its substrates as well as the impact of mutations of FBXW7 on cancer development. We also address the clinical potential of anticancer therapy targeting FBXW7.

Keywords: Cancer stem cells; Chemoresistance; FBXW7; Mutations in cancer; Ubiquitin-Proteasome system.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Drug Resistance, Neoplasm / genetics
F-Box-WD Repeat-Containing Protein 7 / genetics*
F-Box-WD Repeat-Containing Protein 7 / metabolism*
Female
Gene Expression Regulation
Genes, Tumor Suppressor*
Humans
Male
Mice, Knockout
Mutation*
Neoplasms / drug therapy
Neoplasms / genetics*
Neoplasms / pathology

Substances

F-Box-WD Repeat-Containing Protein 7
FBXW7 protein, human
Fbxw7 protein, mouse