» Articles » PMID: 34760892

Tumor Suppressor FBXW7 and Its Regulation of DNA Damage Response and Repair

Overview
Specialty Cell Biology
Date 2021 Nov 11
PMID 34760892
Citations 9
Authors
Affiliations
Soon will be listed here.
Abstract

The proper DNA damage response (DDR) and repair are the central molecular mechanisms for the maintenance of cellular homeostasis and genomic integrity. The abnormality in this process is frequently observed in human cancers, and is an important contributing factor to cancer development. FBXW7 is an F-box protein serving as the substrate recognition component of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase. By selectively targeting many oncoproteins for proteasome-mediated degradation, FBXW7 acts as a typical tumor suppressor. Recent studies have demonstrated that FBXW7 also plays critical roles in the process of DDR and repair. In this review, we first briefly introduce the processes of protein ubiquitylation by SCF and DDR/repair, then provide an overview of the molecular characteristics of FBXW7. We next discuss how FBXW7 regulates the process of DDR and repair, and its translational implication. Finally, we propose few future perspectives to further elucidate the role of FBXW7 in regulation of a variety of biological processes and tumorigenesis, and to design a number of approaches for FBXW7 reactivation in a subset of human cancers for potential anticancer therapy.

Citing Articles

The HTLV-I oncoprotein Tax inactivates the tumor suppressor FBXW7.

Bellon M, Yeh C, Bai X, Nicot C J Virol. 2024; 98(7):e0040524.

PMID: 38874362 PMC: 11264933. DOI: 10.1128/jvi.00405-24.


The Role of FBXW7 in Gynecologic Malignancies.

Di Fiore R, Suleiman S, Drago-Ferrante R, Subbannayya Y, Suleiman S, Vasileva-Slaveva M Cells. 2023; 12(10).

PMID: 37408248 PMC: 10216672. DOI: 10.3390/cells12101415.


Comprehensive characterization of FBXW7 mutational and clinicopathological profiles in human colorectal cancers.

Liu Y, Chen H, Bao H, Zhang J, Wu R, Zhu L Front Oncol. 2023; 13:1154432.

PMID: 37064111 PMC: 10091464. DOI: 10.3389/fonc.2023.1154432.


Different miRNAs Related to Mutations or High Mitotic Indices Contribute to Rectal Neuroendocrine Tumors: A Pilot Study.

Kang H, Park H, Lim H, Son I, Kim M, Kim N Int J Mol Sci. 2023; 24(7).

PMID: 37047300 PMC: 10093831. DOI: 10.3390/ijms24076329.


An innate pathogen sensing strategy involving ubiquitination of bacterial surface proteins.

Apte S, Bhutda S, Ghosh S, Sharma K, Barton T, Dibyachintan S Sci Adv. 2023; 9(12):eade1851.

PMID: 36947610 PMC: 10032600. DOI: 10.1126/sciadv.ade1851.


References
1.
Yada M, Hatakeyama S, Kamura T, Nishiyama M, Tsunematsu R, Imaki H . Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J. 2004; 23(10):2116-25. PMC: 424394. DOI: 10.1038/sj.emboj.7600217. View

2.
Wu R, Feng Q, Lonard D, OMalley B . SRC-3 coactivator functional lifetime is regulated by a phospho-dependent ubiquitin time clock. Cell. 2007; 129(6):1125-40. DOI: 10.1016/j.cell.2007.04.039. View

3.
Zhang H, Shao F, Guo W, Gao Y, He J . Knockdown of KLF5 promotes cisplatin-induced cell apoptosis via regulating DNA damage checkpoint proteins in non-small cell lung cancer. Thorac Cancer. 2019; 10(5):1069-1077. PMC: 6501027. DOI: 10.1111/1759-7714.13046. View

4.
Sheng W, LaFleur M, Nguyen T, Chen S, Chakravarthy A, Conway J . LSD1 Ablation Stimulates Anti-tumor Immunity and Enables Checkpoint Blockade. Cell. 2018; 174(3):549-563.e19. PMC: 6063761. DOI: 10.1016/j.cell.2018.05.052. View

5.
Galli F, Rossi M, DAlessandra Y, De Simone M, Lopardo T, Haupt Y . MDM2 and Fbw7 cooperate to induce p63 protein degradation following DNA damage and cell differentiation. J Cell Sci. 2010; 123(Pt 14):2423-33. DOI: 10.1242/jcs.061010. View