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

Marc Piechaczyk

Education

  • 1981: PhD in Biochemistry, University of Sciences of Montpellier, France.

Research Appointments

  • 2001: Director of the Institute of Molecular Genetics of Montpellier (IGMM).
  • 1993: Founding member and group leader at IGMM.
  • 1991: P: Director of Research at the CNRS (French National Center for Scientific Research).
  • 1983: Senior Researcher at the CNRS.
Marc Piechaczyk

Research Interests

We interested at both better understanding cancer and improving its treatments.

More specifically, we are studying the involvement of various transcription factors in this disease, as those constitute essential molecular platforms for the integration of intra- and extracellular signals thorugh regulation of their activity by post-translational modifications such as phosphorylation, ubiquitylation and sumoylation.

In this context, we are addressing two complementary issues. First, we are investigating why and how two proteins related to the c-Fos proto-oncoprotein, Fra-1 and Fra-2, contribute to the metastatic phenotype in the breast tumors where they are overexpressed in hyperphosphorylated due to perverted cell signalling. This question is particularly important as metastatic breast cancer is the main cause of death by cancer amongst women. Secondly, we are studying how redox metabolism and transcription factor sumoylation, a post-transcriptional modification related to ubiquitin often altered in tumors, control the expression of transcriptomes and are involved in tumorigenesis and resistance to chemotherapies. To this aim, we are combining large-scale genomic and transcriptomic approaches to functional studies, both in vitro and in vivo in mouse models as well as using patient samples, with a special emphasis on leukemia with bad prognosis.

Keywords: breast cancer, leukemia, chemotherapy, Fos, Jun, AP-1, SUMO, ubiquitin/proteasome, cell signalling, transcriptome, large-scale genomic studies, redox metabolism

Figure 1. Protein of the Fos family accumulating in the nucleus (yellow), contrasting with a protein freely diffusing between the nucleus and the cytoplasm (red). Both intranuclear and intracellular distribution and dynamics of Fos and Jun proteins are regulated by phosphorylation, ubiquitylation and sumoylation.

Selected Publications

Talotta F, Mega T, Bossis G, Casalino L, Basbous J, Jariel-Encontre I, Piechaczyk M, Verde P. Heterodimerization with Fra-1 cooperates with the ERK pathway to stabilize c-Jun in response to the RAS oncoprotein. Oncogene. 2010 29(33):4732-4 http://www.ncbi.nlm.nih.gov/pubmed/20543861

Michaud HA, Gomard T, Gros L, Thiolon K, Nasser R, Jacquet C, Hernandez J, Piechaczyk M, Pelegrin M. A crucial role for infected-cell/antibody immune complexes in the enhancement of endogenous antiviral immunity by short passive immunotherapy. PLoS Pathog. 2010 Jun 10;6(6):e1000948. http://www.ncbi.nlm.nih.gov/pubmed/20548955

Gomard T, Michaud HA, Tempé D, Thiolon K, Pelegrin M, Piechaczyk M. An NF-kappaB-dependent role for JunB in the induction of proinflammatory cytokines in LPS-activated bone marrow-derived dendritic cells. PLoS One. 2010 Mar 8;5(3):e9585. http://www.ncbi.nlm.nih.gov/pubmed/20548955

Malnou CE, Brockly F, Favard C, Moquet-Torcy G, Piechaczyk M, Jariel-Encontre I. Heterodimerization with different Jun proteins controls c-Fos intranuclear dynamics and distribution. J Biol Chem. 2010 285(9):6552-62. http://www.ncbi.nlm.nih.gov/pubmed/20053986

Jariel-Encontre I, Bossis G, Piechaczyk M. Ubiquitin-independent degradation of proteins by the proteasome. Biochim Biophys Acta. 2008 Dec;1786(2):153-77. http://www.ncbi.nlm.nih.gov/pubmed/18558098

Garaude J, Farrás R, Bossis G, Charni S, Piechaczyk M, Hipskind RA, Villalba M. SUMOylation regulates the transcriptional activity of JunB in T lymphocytes. J Immunol. 2008 180(9):5983-90. http://www.ncbi.nlm.nih.gov/pubmed/18424718

Baldin V, Militello M, Thomas Y, Doucet C, Fic W, Boireau S, Jariel-Encontre I, Piechaczyk M, Bertrand E, Tazi J, Coux O. A novel role for PA28gamma-proteasome in nuclear speckle organization and SR protein trafficking. Mol Biol Cell. 2008 19(4):1706-16. http://www.ncbi.nlm.nih.gov/pubmed/18256291

Malnou CE, Salem T, Brockly F, Wodrich H, Piechaczyk M, Jariel-Encontre I. Heterodimerization with Jun family members regulates c-Fos nucleocytoplasmic traffic. J Biol Chem. 2007 Oct 19;282(42):31046-59. http://www.ncbi.nlm.nih.gov/pubmed/17681951

Basbous J, Chalbos D, Hipskind R, Jariel-Encontre I, Piechaczyk M. Ubiquitin-independent proteasomal degradation of Fra-1 is antagonized by Erk1/2 pathway-mediated phosphorylation of a unique C-terminal destabilizer. Mol Cell Biol. 2007 27(11):3936-50. http://www.ncbi.nlm.nih.gov/pubmed/17371847

Partner

IGMM

Fellow

Marko Ristic

Additional information

Laboratory Web Page: www.igmm.cnrs.fr