Welcome to Proteasome Lab at NCCS !

Ubiquitin landscape in the eukaryotic cell is vast and complicated which orchestrate most of the cellular signaling pathways. The ubiquitination status of a protein -- the number of ubiquitin attachments, nature of polyubiquitin type, linkage and topology -- plays the critical role for its cellular function. The precise regulation for modulating this landscape is executed by a fine balance between ubiquitination and deubiquitination via the actions of E3 ligases (>600) and DUBs (>100). We aim to understand the cumulative as well as individual contribution of the E3 ligases and DUBs towards maintaining a healthy proteoform by following Proteomic, Ubiquitinomic and biochemical approaches.

In our recent past studies, we have uncovered the adaptive response of hypoxic cells to regulate protein degradation. Interestingly we observed that the free 20S proteasomes can also degrade the ubiquitinated proteins, but without releasing the ubiquitin units unlike 26S proteasomes does. The 20S proteasomes do not have any unfoldase activities. So, this surprising ability of 20S proteasome in unfolding globular proteins is far from our current understanding. We follow a structural and biochemical approach to understand the events of substrate recognition, binding, unfolding, translocation and degradation by 20S proteasome.