The underlying hypothesis of the proposed studies is that the ability of activated Cdc42 to induce anchorage-independent growth derives from its effects on cyclin A. Thus, the proposal focuses on identifying the mechanisms by which Cdc42 induces anchorage-independent growth and how it stimulates cyclin A expression in the absence of mitogens. The application contains three specific aims. The first will be to determine the mechanism by which Cdc42 activates the cyclin A promoter. Here the goal will be to identify and characterize the cis- and trans-acting factors that confer Cdc42-responsiveness to the cyclin A promoter.
The second aim i s to identify Cdc42 effectors that are responsible for mediating cyclin A induction and anchorage-independent growth.
The third aim will be to establish whether Cdc42V12 effectors are critical mediators of adhesion-dependent signals during the normal proliferative response. The importance of these experiments is to establish whether similar pathways are used by a transforming Cdc42 mutant and wild type Cdc42 under normal physiological conditions.
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