Implications of FBXW7 in Neurodevelopment and Neurodegeneration: Molecular Mechanisms and Therapeutic Potential

Overview

Journal Front Cell Neurosci

Specialty Cell Biology

Date 2021 Sep 13

PMID 34512273

Citations 13

Authors

Yu Yang

Xuan Zhou

Xinpeng Liu

Ruying Song

Yiming Gao

Shuai Wang

Affiliations

Soon will be listed here.

Abstract

The ubiquitin-proteasome system (UPS) mediated protein degradation is crucial to maintain quantitive and functional homeostasis of diverse proteins. Balanced cellular protein homeostasis controlled by UPS is fundamental to normal neurological functions while impairment of UPS can also lead to some neurodevelopmental and neurodegenerative disorders. Functioning as the substrate recognition component of the SCF-type E3 ubiquitin ligase, FBXW7 is essential to multiple aspects of cellular processes via targeting a wide range of substrates for proteasome-mediated degradation. Accumulated evidence shows that FBXW7 is fundamental to neurological functions and especially implicated in neurodevelopment and the nosogenesis of neurodegeneration. In this review, we describe general features of FBXW7 gene and proteins, and mainly present recent findings that highlight the vital roles and molecular mechanisms of FBXW7 in neurodevelopment such as neurogenesis, myelination and cerebral vasculogenesis and in the pathogenesis of some typical neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Additionally, we also provide a prospect on focusing FBXW7 as a potential therapeutic target to rescue neurodevelopmental and neurodegenerative impairment.

Citing Articles

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References

Chitnis A, Henrique D, Lewis J, Ish-Horowicz D, Kintner C . Primary neurogenesis in Xenopus embryos regulated by a homologue of the Drosophila neurogenic gene Delta. Nature. 1995; 375(6534):761-6. DOI: 10.1038/375761a0. View

Ko Y, Song H, Kim W, Yune T, Yun N, Oh Y . Calpain-mediated cleavage of Fbxw7 during excitotoxicity. Neurosci Lett. 2020; 736:135265. DOI: 10.1016/j.neulet.2020.135265. View

Min S, Lau A, Lee T, Inuzuka H, Wei S, Huang P . Negative regulation of the stability and tumor suppressor function of Fbw7 by the Pin1 prolyl isomerase. Mol Cell. 2012; 46(6):771-83. PMC: 3389221. DOI: 10.1016/j.molcel.2012.04.012. View

Wang X, Zhai H, Wang F . 6-OHDA Induces Oxidation of F-box Protein Fbw7β by Chaperone-Mediated Autophagy in Parkinson's Model. Mol Neurobiol. 2017; 55(6):4825-4833. DOI: 10.1007/s12035-017-0686-0. View

Song W, Chen J, Petrilli A, Liot G, Klinglmayr E, Zhou Y . Mutant huntingtin binds the mitochondrial fission GTPase dynamin-related protein-1 and increases its enzymatic activity. Nat Med. 2011; 17(3):377-82. PMC: 3051025. DOI: 10.1038/nm.2313. View

Chang H, Liu Y, Wang L, Wang J, Zhao Z, Qu J . MiR-182 promotes cell proliferation by suppressing FBXW7 and FBXW11 in non-small cell lung cancer. Am J Transl Res. 2018; 10(4):1131-1142. PMC: 5934572. View

Pohl C, Dikic I . Cellular quality control by the ubiquitin-proteasome system and autophagy. Science. 2019; 366(6467):818-822. DOI: 10.1126/science.aax3769. View

Sato A . mTOR, a Potential Target to Treat Autism Spectrum Disorder. CNS Neurol Disord Drug Targets. 2016; 15(5):533-43. PMC: 5070418. DOI: 10.2174/1871527315666160413120638. View

Chen Z, Su X, Shen Y, Jin Y, Luo T, Kim I . MiR322 mediates cardioprotection against ischemia/reperfusion injury via FBXW7/notch pathway. J Mol Cell Cardiol. 2019; 133:67-74. PMC: 6629474. DOI: 10.1016/j.yjmcc.2019.05.020. View

10.

Cao S, Wang Y, Li J, Lv M, Niu H, Tian Y . Tumor-suppressive function of long noncoding RNA MALAT1 in glioma cells by suppressing miR-155 expression and activating FBXW7 function. Am J Cancer Res. 2016; 6(11):2561-2574. PMC: 5126273. View

11.

Peng G, Yang C, Liu Y, Shen C . miR-25-3p promotes glioma cell proliferation and migration by targeting FBXW7 and DKK3. Exp Ther Med. 2019; 18(1):769-778. PMC: 6566094. DOI: 10.3892/etm.2019.7583. View

12.

Chernousov M, Yu W, Chen Z, Carey D, Strickland S . Regulation of Schwann cell function by the extracellular matrix. Glia. 2008; 56(14):1498-1507. DOI: 10.1002/glia.20740. View

13.

Harrigan J, Jacq X, Martin N, Jackson S . Deubiquitylating enzymes and drug discovery: emerging opportunities. Nat Rev Drug Discov. 2017; 17(1):57-78. PMC: 7097658. DOI: 10.1038/nrd.2017.152. View

14.

Ji S, Qin Y, Shi S, Liu X, Hu H, Zhou H . ERK kinase phosphorylates and destabilizes the tumor suppressor FBW7 in pancreatic cancer. Cell Res. 2015; 25(5):561-73. PMC: 4423074. DOI: 10.1038/cr.2015.30. View

15.

Hua Y, Zhao K, Tao G, Dai C, Su Y . miR-25 promotes metastasis via targeting FBXW7 in esophageal squamous cell carcinoma. Oncol Rep. 2017; 38(5):3030-3038. DOI: 10.3892/or.2017.5995. View

16.

Xu D, Yao M, Wang Y, Yuan L, Hoeck J, Yu J . MEKK3 coordinates with FBW7 to regulate WDR62 stability and neurogenesis. PLoS Biol. 2018; 16(12):e2006613. PMC: 6347294. DOI: 10.1371/journal.pbio.2006613. View

17.

Gu Z, Inomata K, Mitsui H, Horii A . Promoter hypermethylation is not the major mechanism for inactivation of the FBXW7 beta-form in human gliomas. Genes Genet Syst. 2008; 83(4):347-52. DOI: 10.1266/ggs.83.347. View

18.

Li W, Bengtson M, Ulbrich A, Matsuda A, Reddy V, Orth A . Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signaling. PLoS One. 2008; 3(1):e1487. PMC: 2198940. DOI: 10.1371/journal.pone.0001487. View

19.

Spruck C, Strohmaier H, Sangfelt O, Muller H, Hubalek M, Muller-Holzner E . hCDC4 gene mutations in endometrial cancer. Cancer Res. 2002; 62(16):4535-9. View

20.

Martin J, WEBSTER H . Mitotic Schwann cells in developing nerve: their changes in shape, fine structure, and axon relationships. Dev Biol. 1973; 32(2):417-31. DOI: 10.1016/0012-1606(73)90251-0. View