Ubiquitylation of unphosphorylated c-myc by novel E3 ligase SCFFbxl8
| Autor: | Sagar Bajpai, Hong Ri Jin, Bartosz Mucha, J. Alan Diehl |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Cancer Biology & Therapy, Vol 23, Iss 1, Pp 348-357 (2022) |
| Druh dokumentu: | article |
| ISSN: | 1538-4047 1555-8576 15384047 |
| DOI: | 10.1080/15384047.2022.2061279 |
| Popis: | Overexpression 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. SCFFbxl8 binds 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. |
| Databáze: | Directory of Open Access Journals |
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