Temporal control of acute protein aggregate turnover by UBE3C and NRF1-dependent proteasomal pathways.

ABSTRACT: A hallmark of neurodegenerative diseases is the progressive loss of proteostasis, leading to the accumulation of misfolded proteins or protein aggregates, with subsequent cytotoxicity. To combat this toxicity, cells have evolved degradation pathways (ubiquitin-proteasome system and autophagy) that detect and degrade misfolded proteins. However, studying the underlying cellular pathways and mechanisms has remained a challenge, as formation of many types of protein aggregates is asynchronous, with individual cells displaying distinct kinetics, thereby hindering rigorous time-course studies. Here, we merge a kinetically tractable and synchronous agDD-GFP system for aggregate formation with targeted gene knockdowns, to uncover degradation mechanisms used in response to acute aggregate formatio

SUBMITTER: Hickey KL 

PROVIDER: S-EPMC11398357 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature