From the Lab of Professor Michael Glickman
20S Proteasome gain-of-functionduring stress conditions
The Proteasome is a large Protein complexresponsible for protein degradation in cells. The 26S Proteasome is composed oftwo main parts – the 19S is the regulatory particle and the 20S which is thecatalytic core particle. Under normal conditions, proteins are ubiquitinated andthen recognized as a substrates for degradation by the 19S, which prepares themfor proteolysis within the 20S subcomplex.However, during stress condition as more proteins are damaged they couldoverload the ubiquitin-proteasome system. Also, during stress, the proteasomeitself could be modified or damaged. We found preliminary evidence that hypoxiaor oxidative stress conditions promote separation of the 19S from the 20S.Recent studies have shown the ability of the 20S to degrade non-ubiquitinatedproteins. We propose a gain-of-function of the 20S during stress conditionsthat could help clearing damaged or partially unfolded proteins. In our work weshow the effect of hypoxia on proteasome composition in the cell and theability of purified human proteasome to degrade a partially unfolded modelsubstrate.