Objective
JunB belongs to the family of AP-l transcription factors, some of which have been shown to play a critical role in the development of a variety of neoplasia. JunB is a negative regulator of cell proliferation which has recently been shown to have a tumor supressor activity in vivo. It is a metabolically unstable protein whose degradation is dramatically accelerated upon phosphorylation, most probably by the cyclinB/cdc2 kinase, in mitosis. JunB is an antagonist of c-Jun, another member of the AP-l family involved in the positive control of important cell cycle Regulators such as cyclin Dl. Consequently, it is believed that its destruction in mitosis is necessary for optimum activity of c-Jun during the Gl phase and proper progression from Gl to S phase in response to mitogenic activation. The molecular basis of the variations in JunB abundance during the cell cycle are still ill-defined. It is Therefore essential to elucidate how JunB is degraded for understanding its physiological functions but also because the cells components participating to its destruction are potential oncogenes since unphysiological degradation is a potential loss of function mechanism. Using a variety of molecular and cellular approaches, I thus propose to decipher the intimate mechanisms whereby JunB is degraded during mitosis with a particular attention to the ubiquitin/proteasome system. I will also investigate the precise timing of JunB degradation in M phase with recently developed microscopic techniques. Together with the development of the degradation-resistant mutants, these experiments will provided an experimental basis for determining whether JunB degradation in mitosis is necessary for proper progression through the cell cycle.
Fields of science
Topic(s)
Data not availableCall for proposal
Data not availableFunding Scheme
RGI - Research grants (individual fellowships)Coordinator
34293 Montpellier
France
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