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Targeting the MYC Ubiquitination-Proteasome Degradation Pathway for Cancer Therapy

Overview
Journal Front Oncol
Specialty Oncology
Date 2021 Jun 28
PMID 34178666
Citations 22
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Abstract

Deregulated MYC overexpression and activation contributes to tumor growth and progression. Given the short half-life and unstable nature of the MYC protein, it is not surprising that the oncoprotein is highly regulated diverse posttranslational mechanisms. Among them, ubiquitination dynamically controls the levels and activity of MYC during normal cell growth and homeostasis, whereas the disturbance of the ubiquitination/deubiquitination balance enables unwanted MYC stabilization and activation. In addition, MYC is also regulated by SUMOylation which crosstalks with the ubiquitination pathway and controls MYC protein stability and activity. In this mini-review, we will summarize current updates regarding MYC ubiquitination and provide perspectives about these MYC regulators as potential therapeutic targets in cancer.

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References
1.
Byun W, Jin M, Yu J, Kim W, Song J, Chung H . A novel selenonucleoside suppresses tumor growth by targeting Skp2 degradation in paclitaxel-resistant prostate cancer. Biochem Pharmacol. 2018; 158:84-94. DOI: 10.1016/j.bcp.2018.10.002. View

2.
Metivier R, Penot G, Hubner M, Reid G, Brand H, Kos M . Estrogen receptor-alpha directs ordered, cyclical, and combinatorial recruitment of cofactors on a natural target promoter. Cell. 2003; 115(6):751-63. DOI: 10.1016/s0092-8674(03)00934-6. View

3.
Morel M, Shah K, Long W . The F-box protein FBXL16 up-regulates the stability of C-MYC oncoprotein by antagonizing the activity of the F-box protein FBW7. J Biol Chem. 2020; 295(23):7970-7980. PMC: 7278360. DOI: 10.1074/jbc.RA120.012658. View

4.
Baluapuri A, Wolf E, Eilers M . Target gene-independent functions of MYC oncoproteins. Nat Rev Mol Cell Biol. 2020; 21(5):255-267. PMC: 7611238. DOI: 10.1038/s41580-020-0215-2. View

5.
Cepeda D, Ng H, Sharifi H, Mahmoudi S, Cerrato V, Fredlund E . CDK-mediated activation of the SCF(FBXO) (28) ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer. EMBO Mol Med. 2013; 5(7):1067-86. PMC: 3721474. DOI: 10.1002/emmm.201202341. View