INPROTEOLYS

Oncogenesis and Immunotherapy

One of the major topics addressed in our laboratory is the regulation and function of the AP-1 transcription complex during the cell cycle and in immune cells. AP-1 is, in fact, a family of dimeric transcription factors, the best known components of which are the members of the Fos and Jun multigene families. It controls most vital cell functions and its dysfunction has various pathological consequences including cancerogenesis. However, depending on the context, certain AP-1 proteins can manifest either oncogenic or anti-oncogenic properties on their own or be necessary mediators of other oncogenes activated upstream. In our lab, we are studying how post-translational modifications control AP-1 protein abundance and activity. Among our most recent observations, one can cite: (i) the demonstration of a proteasome-dependent, but ubiquitin-independent, degradation of two Fos proteins, c-Fos and Fra-1, (ii) the transcriptional repression of c-Fos by sumoylation, the latter being itself subjected to a complex regulation via diverse signaling pathways, including those involving reactive oxygen species, (iii) a particular intracellular and intranuclear dynamics of Fos and Jun proteins and (iv) the requirement of JunB protein in late G2 for proper progression through subsequent mitosis. Our investigations are conducted in physiological systems, such as dividing cells of various sorts and during maturation of dendritic cells by pathogens, and in pathological situations, including different cancers where intracellular signaling is altered. They aim at better understanding the molecular basis of tumorigenesis and of the immune response.

Marc Piechaczyk

Guillaume Bossis

Isabelle Jariel

Denis Tempé

E-mail

marc.piechaczyk@igmm.cnrs.fr

Phone

33 (0)4 67 61 36 68

Fax

33 (0)4 67 04 02 31

Address

IGMM - CNRS -1919, route de Mende - 34293 - Montpellier Cedex 05 - France

Center

Institute of Molecular Genetics of Montpellier (IGMM)

Group Web

http://www.igmm.cnrs.fr/spip.php?rubrique37

Research Lines

 We are following several entangled lines of investigation. These are the study of : - (i) the mechanisms of Fos and Jun protein degradation in normal cells, including those of the immune system, and alteration of these mechanisms in cancer cells, - (ii) the regulation of transcription by sumoylation in normal cells, including those of the immune system, and dysregulation in cancer cells and - (iiii) the relastionships between protein degradation, sumoylation and intracellular signaling, including that affecting the redox status of cells.

Patents

Publications

Pubmed ID: 18424718

Title: SUMOylation Regulates the Transcriptional Activity of JunB in T Lymphocytes.

Authors: Johan Garaude , Rosa Farrás , Guillaume Bossis , Seyma Charni , Marc Piechaczyk , Robert A Hipskind , Martin Villalba ,

Year: 2008

Journal: J Immunol volume: 180 pages: 5983-90

Pubmed ID: 18256291

Title: A Novel Role for PA28{gamma}-Proteasome in Nuclear Speckle Organization and SR Protein Trafficking.

Authors: Véronique Baldin , Muriel Militello , Yann Thomas , Christine Doucet , Weronika Fic , Stephanie Boireau , Isabelle Jariel-Encontre , Marc Piechaczyk , Edouard Bertrand , Jamal Tazi , Olivier Coux ,

Year: 2008

Journal: Mol Biol Cell volume: No volume provided pages:

Pubmed ID: 18391017

Title: JunB breakdown in mid/late G2 is required for down-regulation of cyclin A2 levels and proper mitosis.

Authors: Rosa Farras , Véronique Baldin , Sandra Gallach , Claire Acquaviva , Guillaume Bossis , Isabelle Jariel-Encontre , Marc Piechaczyk ,

Year: 2008

Journal: Mol Cell Biol volume: No volume provided pages:

Pubmed ID: 17371847

Title: Ubiquitin-independent proteasomal degradation of Fra-1 is antagonized by Erk1/2 pathway-mediated phosphorylation of a unique C-terminal destabilizer.

Authors: Jihane Basbous , Dany Chalbos , Robert Hipskind , Isabelle Jariel-Encontre , Marc Piechaczyk ,

Year: 2007

Journal: Mol Cell Biol volume: No volume provided pages:

Pubmed ID: 17825471

Title: Ubiquitin-independent- versus ubiquitin-dependent proteasomal degradation of the c-Fos and Fra-1 transcription factors: Is there a unique answer?

Authors: Jihane Basbous , Isabelle Jariel-Encontre , Tiphanie Gomard , Guillaume Bossis , Marc Piechaczyk ,

Year: 2007

Journal: Biochimie volume: No volume provided pages:

Pubmed ID: 17681951

Title: Heterodimerization with Jun Family Members Regulates c-Fos Nucleocytoplasmic Traffic.

Authors: Cécile E Malnou , Tamara Salem , Frédérique Brockly , Harald Wodrich , Marc Piechaczyk , Isabelle Jariel-Encontre ,

Year: 2007

Journal: J Biol Chem volume: 282 pages: 31046-59

Pubmed ID: 16055710

Title: Down-regulation of c-Fos/c-Jun AP-1 dimer activity by sumoylation.

Authors: Guillaume Bossis , Cécile E Malnou , Rosa Farras , Elisabetta Andermarcher , Robert Hipskind , Manuel Rodriguez , Darja Schmidt , Stefan Muller , Isabelle Jariel-Encontre , Marc Piechaczyk ,

Year: 2005

Journal: Mol Cell Biol volume: 25 pages: 6964-79

Pubmed ID: 15780906

Title: Mechanisms of delivery of ubiquitylated proteins to the proteasome: new target for anti-cancer therapy?

Authors: Rosa Farràs , Guillaume Bossis , Elisabetta Andermarcher , Isabelle Jariel-Encontre , Marc Piechaczyk ,

Year: 2005

Journal: Crit Rev Oncol Hematol volume: 54 pages: 31-51

Pubmed ID: 15210726

Title: SUMOylation regulates nucleo-cytoplasmic shuttling of Elk-1.

Authors: Sara Salinas , Anne Briançon-Marjollet , Guillaume Bossis , Marie-Aude Lopez , Marc Piechaczyk , Isabelle Jariel-Encontre , Anne Debant , Robert A Hipskind ,

Year: 2004

Journal: J Cell Biol volume: 165 pages: 767-73

Pubmed ID: 14517309

Title: c-Fos proto-oncoprotein is degraded by the proteasome independently of its own ubiquitinylation in vivo.

Authors: Guillaume Bossis , Patrizia Ferrara , Claire Acquaviva , Isabelle Jariel-Encontre , Marc Piechaczyk ,

Year: 2003

Journal: Mol Cell Biol volume: 23 pages: 7425-36

Pubmed ID: 12937177

Title: The HBZ factor of human T-cell leukemia virus type I dimerizes with transcription factors JunB and c-Jun and modulates their transcriptional activity.

Authors: Jihane Basbous , Charlotte Arpin , Gilles Gaudray , Marc Piechaczyk , Christian Devaux , Jean-Michel Mesnard ,

Year: 2003

Journal: J Biol Chem volume: 278 pages: 43620-7

Pubmed ID: 12629509

Title: The structural determinants responsible for c-Fos protein proteasomal degradation differ according to the conditions of expression.

Authors: Patrizia Ferrara , Elisabetta Andermarcher , Guillaume Bossis , Claire Acquaviva , Frédérique Brockly , Isabelle Jariel-Encontre , Marc Piechaczyk ,

Year: 2003

Journal: Oncogene volume: 22 pages: 1461-74

Pubmed ID: 12437928

Title: CNF1 exploits the ubiquitin-proteasome machinery to restrict Rho GTPase activation for bacterial host cell invasion.

Authors: Anne Doye , Amel Mettouchi , Guillaume Bossis , René Clément , Caroline Buisson-Touati , Gilles Flatau , Laurent Gagnoux , Marc Piechaczyk , Patrice Boquet , Emmanuel Lemichez ,

Year: 2002

Journal: Cell volume: 111 pages: 553-64

Pubmed ID: 11709728

Title: Identification of a C-terminal tripeptide motif involved in the control of rapid proteasomal degradation of c-Fos proto-oncoprotein during the G(0)-to-S phase transition.

Authors: C Acquaviva , F Brockly , P Ferrara , G Bossis , C Salvat , I Jariel-Encontre , M Piechaczyk ,

Year: 2001

Journal: Oncogene volume: 20 pages: 7563-72

Pubmed ID: 11314029

Title: Cellular and viral Fos proteins are degraded by different proteolytic systems.

Authors: C Acquaviva , C Salvat , F Brockly , G Bossis , P Ferrara , M Piechaczyk , I Jariel-Encontre ,

Year: 2001

Journal: Oncogene volume: 20 pages: 942-50

Pubmed ID: 11313987

Title: Human cyclin C protein is stabilized by its associated kinase cdk8, independently of its catalytic activity.

Authors: C Barette , I Jariel-Encontre , M Piechaczyk , J Piette ,

Year: 2001

Journal: Oncogene volume: 20 pages: 551-62

Collaborations

Facilities

All facilities for molecular biology, biochemistry, cell culture, experiments with mice and a L3 laboratory are available at the IGMM

NEWS

EVENTS

Keywords

Oncogenesis, transcription factors, AP-1, Fos, Jun, protein degradation, ubiquitin, proteasome, sumoylation, gene regulation, cell signalling, retrovirology, immune response, dendritic cells