Amyloid formation and depolymerization of tumor suppressor p16^INK4a are regulated by a thiol-dependent redox mechanism.

ABSTRACT: The conversion of a soluble protein into polymeric amyloid structures is a process that is poorly understood. Here, we describe a fully redox-regulated amyloid system in which cysteine oxidation of the tumor suppressor protein p16^INK4a leads to rapid amyloid formation. We identify a partially-structured disulfide-bonded dimeric intermediate species that subsequently assembles into fibrils. The stable amyloid structures disassemble when the disulfide bond is reduced. p16^INK4a is frequently mutated in cancers and is considered highly vulnerable to single-point mutations. We find that multiple cancer-related mutations show increased amyloid formation propensity whereas mutations stabilizing the fold prevent transition into amyloid. The complex transition into amyloids an

SUBMITTER: Heath SG 

PROVIDER: S-EPMC11217399 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature