Switching of the c-Myc protein degradation pathway depending on the PP2A-B55α complex levels - PubMed
a day ago
- #c-Myc
- #protein degradation
- #PP2A-B55α
- The transcription factor c-Myc is a master oncoprotein regulating over 15% of all genes.
- Protein phosphatase 2A (PP2A) destabilizes c-Myc protein, acting as a crucial tumor suppressor.
- PP2A-B55α complex regulates c-Myc degradation in a biphasic manner: suppression increases Thr58 phosphorylation enhancing FBXW7-dependent degradation, while overexpression promotes UBR5-mediated degradation.
- PP2A-B55α binds and dephosphorylates UBR5, unlike B55δ which shows weaker binding affinity and fails to induce c-Myc degradation.
- The findings identify PP2A-B55α as a context-dependent molecular switch for c-Myc degradation, resolving the paradox of PP2A activation leading to c-Myc destabilization.