description): Reversible protein phosphorylation through the opposing actions of protein kinases and protein phosphatases regulates virtually every aspect of cellular growth and differentiation. There is growing evidence that protein phosphatases have anti-proliferative activity. One PP2A regulatory subunit in particular, B568, appears to be a prime candidate to impart growth inhibitory function. It is the only PP2A subunit that has cell cycle-regulated nuclear localization, moving from the cytoplasm to the nucleus at the end of mitosis. The regulatory, targeting and substrate specificity functions of B568 are likely achieved by protein-protein interactions. The investigators have identified B568 interacting proteins using the yeast two-hybrid system. Their preliminary results are promising as we have several interesting groups of clones including the p53 and TGF-B-regulated cyclins, cyclins G1 and G2; the cargo binding domain of the kinesin-related protein, KIF4, that is likely to function in mitosis; as well as several groups of novel interacting proteins. The interaction of B568 with these potential cell cycle regulatory proteins suggests specific mechanisms by which PP2A modulates cellular proliferation. In an effort to gain further insight into the role of B568 in cellular growth and differentiation, the investigators will: 1) Determine the biologic consequences of the interactions between B568 and its binding protein; and 2) Further characterize the cell cycle regulated nuclear localization of B568 and its role in cell cycle progression.
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