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Junb degradation in mitosis

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.

Funding Scheme

RGI - Research grants (individual fellowships)

Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
Address
Route De Mende 1919
34293 Montpellier
France