Protein Quality Control by the VCP AAA-ATPase
The ubiquitin proteasome system (UPS) is the major regulatory system that maintains the homeostasis of the cellular proteome. It controls the stability, sub-cellular location and activation of a large cross-section of cellular proteins. The multiplicity in ubiquitin function provides immense regulatory capacity not limited to only protein degradation. There is a growing body of work suggesting that capture of polyubiquitin chains on substrates by so-called ‘ubiquitin receptors’ is a well-regulated step critical to many cellular processes. Dysfunction of the UPS particularly at the ubiquitin recognition step can lead to the inappropriate accumulation of substrates, perturbation in the balance of the proteome and proteotoxic stress. Thus, understanding how the UPS system coordinates protein quality control may identify strategies to target vulnerabilities in human disease, especially in protein aggregation disorders.
The latest from the lab...
This weeks journal club paper:
p62 filaments capture and present ubiquitinated cargos for autophagy
Zaffagnini et.al., EMBO 2018
Feb 2018. Salwa Mostafa joins the lab for a rotation!