The proteasome is the proteolytic machinery of the ubiquitin-proteasome system (UPS), the main pathway responsible for degradation of intracellular proteins. As the major cellular protease, the proteasome is a key player in eukaryotic protein homeostasis and dysregulation of the UPS has been involved in cancers but also in inflammatory and neurodegenerative diseases. Because of this, protea­somes have been identified as therapeutic targets, especially for some cancers.

Proteasomes are highly heterogeneous and dynamic protein complexes comprising dozens of subunits and regulatory proteins. The cell adapts proteasome plasticity and dynamics to meet specific subcellular needs or to respond to stress or other stimuli.

The purpose of our project is to carry out a comprehensive study of the proteasome complexes diversity in eukaryotic cells using innovant proteomic and structural strategies based on mass spectrometry, including :

AP-MS and proteomics

Heterogeneity, dynamics
and interactome

Targeted Proteomics

Absolute quantification
and stoichiometry

Structural MS

Dynamics, stoichiometry, PTMs
and interaction interfaces