Investigating the essential roles of Ubiquitin-like molecules and the Ubiquitin Proteasome System

Olivier Coux

Education

  • 1992: PhD at the Université Paris 7, Paris, France.
  • 1999: Habilitation to supervise research, Montpellier 2 University, Montpellier, France

Research Appointments

  • 1998: Group Leader at CRBM-CNRS, Montpellier, France.
  • 1992 - 1997: Postdoctoral Fellow at Harvard Medical School (Prof. A.L. Goldberg), Boston, USA.
Oliver Coux

Research Interests

Our studies aim at a better understanding of the intricate mechanisms by which the ubiquitin-proteasome pathway controls cell proliferation. We follow two main research axes, by a combination of biochemical and cell biology approaches: (i) dissection of the mechanisms regulating the stability of key regulators of cell proliferation, namely the phosphatase CDC25B, cyclin E (CycE) and the oncosuppressive protein p53; (ii) analysis of the functioning and the cellular distribution of the 26S proteasome.

Regarding CDC25B, we recently demonstrated that the protein was particularly unstable at the end of mitosis, and that its uncomplete degradation of CDC25B after metaphase led to unexpected abnormalities. This suggested that unknown substrates of CDC25B were deregulated and our recent work was aimed at their identification. The work on CycE degradation led us to the discovery of a novel mechanism of regulation of the Ubiquitin-ligase responsible for its degradation, the SCFFbw7. Finally, using the state of the art cell imaging facility of Montpellier (http://www.mri.cnrs.fr), an important program of our team is to analyse, using in vivo interaction techniques such as FRET (Fluorescence Resonance Energy Transfer) or FLIM (Fluorescence Lifetime Imaging Microscopy) where in the cell and when during cell cycle the 20S proteasome interacts with its regulators.

Selected Publications

Bonne-Andrea, C., Kahli, M., Mechali, F., Lemaitre, J.-M., Bossis, G. and Coux, O. (2013). SUMO2/3 modification of cyclin E contributes to the control of replication origin firing. Nat Commun 4, 1850. http://www.ncbi.nlm.nih.gov/pubmed/23673635

Biard-Piechaczyk M., Borel S., Espert L., de Bettignies G. and Coux O. (2012). HIV-1, ubiquitin and ubiquitin-like proteins: the dialectic interactions of a virus with a sophisticated network of post-translational modifications. Biol. Cell 104: 165–187. http://www.ncbi.nlm.nih.gov/pubmed/22188301

Wodrich, H., Henaff, D., Jammart, B., Segura-Morales, C., Seelmeir, S., Coux, O., Ruzsics, Z., Wiethoff, C. M., and Kremer, E. J. (2010). A Capsid-Encoded PPxY-Motif Facilitates Adenovirus Entry. PLoS Pathog 6, e1000808. http://www.ncbi.nlm.nih.gov/pubmed/20333243

Thomas, Y., Coux, O., and Baldin, V. (2010). βTrCP-dependent degradation of CDC25B phosphatase at the metaphase-anaphase transition is a pre-requisite for correct mitotic exit. Cell Cycle 9, 4338–4350. http://www.ncbi.nlm.nih.gov/pubmed/21051950

de Bettignies, G., and Coux, O. (2010). Proteasome inhibitors: Dozens of molecules and still counting. Biochimie 92, 1530–1545. http://www.ncbi.nlm.nih.gov/pubmed/20615448

Baldin, V., Militello, M., Thomas, Y., Doucet, C., Fic, W., Boireau, S., Jariel-Encontre, I., Piechaczyk, M., Bertrand, E., Tazi, J., et al. (2008). A novel role for PA28gamma-proteasome in nuclear speckle organization and SR protein trafficking. Mol. Biol. Cell 19, 1706–1716. http://www.ncbi.nlm.nih.gov/pubmed/18256291

Linares, L. K., Kiernan, R., Triboulet, R., Chable-Bessia, C., Latreille, D., Cuvier, O., Lacroix, M., Le Cam, L., Coux, O., and Benkirane, M. (2007). Intrinsic ubiquitination activity of PCAF controls the stability of the oncoprotein Hdm2. Nat. Cell Biol 9, 331–338. http://www.ncbi.nlm.nih.gov/pubmed/17293853

Lassot, I., Latreille, D., Rousset, E., Sourisseau, M., Linares, L. K., Chable-Bessia, C., Coux, O., Benkirane, M., and Kiernan, R. E. (2007). The proteasome regulates HIV-1 transcription by both proteolytic and nonproteolytic mechanisms. Mol Cell 25, 369–383. http://www.ncbi.nlm.nih.gov/pubmed/17289585

Le Cam, L., Linares, L. K., Paul, C., Julien, E., Lacroix, M., Hatchi, E., Triboulet, R., Bossis, G., Shmueli, A., Rodriguez, M. S., et al. (2006). E4F1 is an atypical ubiquitin ligase that modulates p53 effector functions independently of degradation. Cell 127, 775–788. http://www.ncbi.nlm.nih.gov/pubmed/17110336

Partner

CRBM

Collaborator

Michael Glickman

Project

The role and regulation of the proteasome regulator PA28γ.