Junb degradation in mitosis

Ziel

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.

Wissenschaftliches Gebiet

natural sciencesbiological sciencesbiochemistrybiomoleculesproteins

Programm/Programme

FP5-HUMAN POTENTIAL - Programme for research, technological development and demonstration on "Improving the human research potential and the socio-economic knowledge base" (1998-2002)

Thema/Themen

Data not available

Aufforderung zur Vorschlagseinreichung

Data not available

Finanzierungsplan

RGI - Research grants (individual fellowships)

Koordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

EU-Beitrag

Keine Daten

Adresse

Route de Mende 1919
34293 MONTPELLIER
Frankreich

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