Journal
AUTOPHAGY
Volume 18, Issue 4, Pages 783-798Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2021.1956105
Keywords
Aggregates; autophagy; deubiquitinase; misfolded proteins; protein homeostasis; TRIM44; ubiquitin-proteasome system
Categories
Funding
- CPRIT [RP200093]
- NIH [R01CA181319]
Ask authors/readers for more resources
The study reveals TRIM44 as a novel link between the UPS system and autophagy pathway, which enhances aggregate protein clearance rate by promoting SQSTM1/p62 oligomerization and binding of K48 ubiquitin chains.
Until recently, the ubiquitin-proteasome system (UPS) and macroautophagy/autophagy were considered to be two independent systems that target proteins for degradation by proteasomes or via lysosomes, respectively. Here, we report that TRIM44 (tripartite motif containing 44) is a novel link that connects the UPS system with the autophagy degradation pathway. Suppressing the UPS degradation pathway leads to TRIM44 upregulation, which further promotes aggregated protein clearance through the binding of K48 ubiquitin chains on proteins. TRIM44 expression activates autophagy via promoting SQSTM1/p62 oligomerization, which rapidly increases the rate of aggregate protein removal. Overall, our data reveal that TRIM44 is a newly identified link between the UPS system and the autophagy pathway. Delineating the cross-talk between these two degradation pathways may reveal new mechanisms of targeting aggregate-prone diseases, such as cancer and neurodegenerative disease.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available