Rapid Isolation of CDK4/Cyclin D Inhibitory Peptides

Most human cancers carry molecular rearrangements of the critical apparatus that control cell divisinstances, two recently identified cell cycle inhibitors, p21/Waf1/Cip1 and p16/Ink4, failed to accunegative growth signals, leading to the uncontrolled proliferation characteristic of cancer cells. Dthis grant, our experimental work will focus on the development of a novel yeast genetic system whicidentification and characterization of short, hexameric peptide sequences that interact with Cdk4/Cyaction of p16/Ink4. Cancer cells in which the activity of the Cdk4/Cyclin D1 kinase is upregulated doverexpression or lack of p16/Ink4, remain exquisitely sensitive to the inhibition of Cyclin D1 funcantibody/antisense microinjection. In Phase II the inhibitory peptides will be further characterizedchemical modification to generate pharmacologically active derivatives. This research will lead to thighly specific antiproliferative agents.