Periodical
Ubiquitylation of unphosphorylated c-myc by novel E3 ligase SCFFbxl8
العنوان: | Ubiquitylation of unphosphorylated c-myc by novel E3 ligase SCFFbxl8 |
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المؤلفون: | Bajpai, Sagar, Jin, Hong Ri, Mucha, Bartosz, Diehl, J. Alan |
المصدر: | Cancer Biology and Therapy; December 2022, Vol. 23 Issue: 1 p348-357, 10p |
مستخلص: | ABSTRACTOverexpression of c-myc via increased transcription or decreased protein degradation is common to many cancer etiologies. c-myc protein degradation is mediated by ubiquitin-dependent degradation, and this ubiquitylation is regulated by several E3 ligases. The primary regulator is Fbxw7, which binds to a phospho-degron within c-myc. Here, we identify a new E3 ligase for c-myc, Fbxl8 (F-box and Leucine Rich Repeat Protein 8), as an adaptor component of the SCF (Skp1-Cullin1-F-box protein) ubiquitin ligase complex, for selective c-myc degradation. SCFFbxl8binds and ubiquitylates c-myc, independent of phosphorylation, revealing that it regulates a pool of c-myc distinct from SCFFbxw7. Loss of Fbxl8 increases c-myc protein levels, protein stability, and cell division, while overexpression of Fbxl8 reduces c-myc protein levels. Concurrent loss of Fbxl8 and Fbxw7 triggers a robust increase in c-myc protein levels consistent with targeting distinct pools of c-myc. This work highlights new mechanisms regulating c-myc degradation. |
قاعدة البيانات: | Supplemental Index |
تدمد: | 15384047 15558576 |
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DOI: | 10.1080/15384047.2022.2061279 |