Team Leader : Laurent Le Cam
Institut de Recherche en
Cancérologie de Montpellier
CRLC Val d’Aurelle-Paul Lamarque
34298 Montpellier cedex 5 |
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Tél. 33 (0)4 67 61 23 49
Fax 33 (0)4 67 61 37 87
laurent.lecam@inserm.fr |
Research topics
Our laboratory is interested in the molecular circuitries implicated in cellular senescence and stem cell activities, and how deregulation of these biological processes affects organismal aging and tumorigenesis.
One of our main research topic includes the characterization of new regulatory mechanisms of the p53 pathway. Functional inactivation of the p53 pathway occurs in most, if not all, human tumors, and deregulation of p53 activities is also associated with premature aging phenotypes. More specifically, we are investigating the roles of the multifunctional protein E4F1 in the p53 pathway. E4F1 was originally identified as a cellular transcription factor targeted by the E1A viral oncoprotein, but our data indicate that E4F1 is also an atypical ubiquitin E3 ligase for other transcription factors, including the p53 tumor suppressor. Data from several laboratories indicate that E4F1 is implicated in several pathways that are essential for cellular senescence and are commonly deregulated during tumorigenesis, including the p53 and Rb tumor suppressor pathways. This project led us to investigate the roles of post-translational modifications implicating the Ubiqutin and ubiquitin-like proteins (Sumo, Nedd8, etc...) in the regulation of several key components of those pathways. Over the past years, we developed several complementary approaches, including the generation of genetically engineered mouse models, to decipher the roles of E4F1 during normal development, aging and tumorigenesis.
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Main Publications
Laëtitia K. Linares, Rosemary Kiernan, Robinson Triboulet, Christine Chable-Bessia, Daniel Latreille, Olivier Cuvier, Matthieu Lacroix, Laurent Le Cam, Olivier Coux, and Monsef Benkirane. (2006). Intrinsic ubiquitylation activity of PCAF controls the stability of the oncoprotein Hdm2. Nat Cell Biol. 2007 Mar; 9(3):331-8.
Le Cam L, Linares LK, Paul C, Julien E, Lacroix M, Hatchi E, Triboulet R, Bossis G, Shmueli A, Rodriguez MS, Coux O, Sardet C. (2006). E4F1 is an atypical ubiquitin ligase that modulates p53 effector functions independently of degradation. Cell. Nov17;127(4):775-88.
Paul C, Lacroix M, Iankova I, Julien E, Schafer BW, Labalette C, Wei Y, Le Cam A, Le Cam L, Sardet C. (2006). The LIM-only protein FHL2 is a negative regulator of E4F1. Oncogene. 2006 Sep 7;25(40):5475-84.
Le Cam L, Lacroix M, Ciemerych MA, Sardet C, Sicinski P. (2004)
The E4F protein is required for mitotic progression during embryonic cell cycles. Mol Cell Biol. 24(14):6467-75.
Sicinska E, Aifantis I, Le Cam L., Swat W, Borowski C, Yu Q, Ferrando AA, Levin SD, Geng Y, von Boehmer H, Sicinski P. (2003) Requirement for cyclin D3 in lymphocyte development and T cell leukemias.
Cancer Cell. Dec;4(6):451-61.
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