| Title: |
Ubiquitylation of unphosphorylated c-myc by novel E3 ligase SCFFbxl8. |
| Authors: |
Bajpai, Sagar1 (AUTHOR), Jin, Hong Ri1 (AUTHOR), Mucha, Bartosz2 (AUTHOR), Diehl, J. Alan2 (AUTHOR) jad283@case.edu |
| Source: |
Cancer Biology & Therapy. 2022, Vol. 23 Issue 1, p348-357. 10p. |
| Subject Terms: |
*UBIQUITIN ligases, *UBIQUITINATION, *PROTEOLYSIS, *PROTEIN stability, *ETIOLOGY of cancer |
| Abstract: |
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. [ABSTRACT FROM AUTHOR] |
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