RAB40C regulates RACK1 stability via the ubiquitin-proteasome system.
Aim
RACK1 is a multifunctional scaffolding protein that is expressed in many cellular compartments, orchestrating a number of signaling processes. RACK1 acts as a signaling hub to localize active enzymes to discrete locations; therefore tight control of RACK1 is vital to cellular homeostasis. Our aim was to identify the mechanisms responsible for RACK1 turnover and show that degradation is directed by the ubiquitin proteasome system.


Results
Using siRNA screening, we identified RAB40C as the ubiquitin E3 ligase responsible for ubiquitination of RACK1, and that the action of RAB40C in controlling RACK1 levels is crucial to both cancer cell growth and migration of T cells.


Conclusion
Our data suggest that manipulation of RACK1 levels in this way may provide a novel strategy to explore RACK1 function.
['Day|Jon P|JP|', 'Whiteley|Ellanor|E|', 'Freeley|Michael|M|', 'Long|Aideen|A|', 'Malacrida|Beatrice|B|', 'Kiely|Patrick|P|', 'Baillie|George S|GS|']
RAB40C RACK1 ubiquitin–proteasome system