Adrien Rousseau's Research Group

Pubmed | Biography

Signalling pathways controlling proteasome homeostasis

Accumulation of unfolded, misfolded, or damaged proteins is deleterious to cells. To avoid such potentially harmful conditions, cells have evolved efficient protein quality control systems which act in a concerted manner to maintain proteostasis. Among them, the ubiquitin-proteasome system (UPS) is one of the major systems in charge of the degradation of short-lived, damaged and misfolded proteins, which makes it a pivotal player in the regulation of various cellular functions. Increasing evidence reveals that alterations and mutations in components of the UPS, are an underlying cause of various age-related diseases, most prominently cancers and neurodegenerative disorders.

The goal of our lab is to unravel the crosstalk between protein phosphorylation and proteasomal degradation, especially how phosphorylation regulates protein degradation to meet the cell’s requirements. We are also aiming at developing new tools to decipher how the proteasome is regulated in cells as well as to identify new drugs and regulators modulating its function. Both yeast and mammalian systems are used to tackle these questions.

We have recently identified an evolutionarily conserved pathway controlling proteasome homeostasis, with TORC1 inhibition inducing the levels of 19S regulatory particle assembly chaperones (RACs) and the assembly of the 26S proteasome under stressful conditions. Downstream of TORC1 inhibition, the kinase Mpk1 orchestrates the inductions of RACs and proteasome assembly. This work illustrates that proteasomal degradation is regulated under stressful conditions, an essential adaptive mechanism for cells to survive. Thus, understanding how cells adapt protein degradation to the needs might help to identify new therapeutic targets to rescue proteostasis defects in diseases.

Back row (L-R): Thomas Williams, Aurellia Winaya, Ailsa Black.  Front Row (L-R) Zhi-Hui Chen, Adrien Rousseau, Ifeoluwapo Joshua
Back row (L-R): Thomas Williams, Aurellia Winaya, Ailsa Black. Front Row (L-R) Zhi-Hui Chen, Adrien Rousseau, Ifeoluwapo Joshua


Flavie Soubigou | Research Technician and MSc Student
Ifeoluwapo Joshua | Postdoctoral Researcher

Selected Publications

  • Agrotis A, Lamoliatte F, Williams TD, Black A, Horberry R, Rousseau A (2023) Multiple phosphorylation of the Cdc48/p97 cofactor protein Shp1/p47 occurs upon cell stress in budding yeast Life Sciences Alliance 6 doi:10.26508/lsa.202201642 PMID: 36693698
  • Williams, T., Cacioppo, R., Agrotis, A., Black, A., Zhou, H., & Rousseau, A (2022) Actin remodelling controls proteasome homeostasis upon stress Nature Cell Biology  doi:10.1038/s41556-022-00938-4 PMID: 35739319
  • Adrien Rousseau and Anne Bertolotti (2016) An evolutionarily conserved pathway controls proteasome homeostasis. Nature 536 184–189 PMID: 27462806
  • Ariane Hanssum, Zhen Zhong, Adrien Rousseau, Agnieszka Krzyzosiak, Anna Sigurdardottir and Anne Bertolotti (2014) An inducible chaperone adapts proteasome assembly to stress Mol. Cell  55 566–577 PMID: 25042801
  • Adrien Rousseau, Alastair Mc Ewen, Pierre Poussin, Didier Rognan, Yves Nominé, Marie-Christine Rio, Catherine Tomasetto and Fabien Alpy (2013) TRAF4 is a novel phosphoinositides binding protein modulating tight junctions and favoring cell migration PLoS Biol 11(12) e1001726 PMID: 24311986
  • Adrien Rousseau & Anne Bertolotti (2018) Regulation of proteasome assembly and activity in health and disease  19(11) 697-712
  • Williams, T. D., Winaya, A., Joshua, I., & Rousseau, A (2023) Proteasome assembly chaperone translation upon stress requires Ede1 phase separation at the plasma membrane iScience 27 doi:10.1016/j.isci.2023.108732 PMID: 38235332
  • Adrien Rousseau, Catherine Tomasetto and Fabien Alpy (2014) The phosphoinositide-binding protein TRAF4 modulates tight junction stability and migration of cancer cells Tissue Barriers  2 e975597 PMID: 25610759