[Cdk inhibiting proteins]

Mammalian cell growth is governed by a number of extracellular signals, among which anti-proliferative stimuli arrest cells in G1 phase of the cell cycle by increasing the activity of a group of polypeptides called cdk inhibitors (cdk inhibiting proteins). So far seven members of cdk inhibiting proteins have been isolated and characterized. They mostly locate in the nucleus and inhibit G1 cyclin/cdk activities by directly binding to them, thereby interfering with phosphorylation of key substrates to exit G1 including retinoblastoma proteins among them. Some of the cdk inhibiting protein genes are frequently deleted or mutated in tumor cells, and certain oncoproteins encoded by transforming viruses target cdk inhibiting proteins, suggesting that cdk inhibiting proteins function as tumor suppressors. It is important to investigate signaling pathways and regulatory mechanisms involving cdk inhibiting proteins not only to better understand cellular proliferation, cell cycle regulation, or cancer development, but also to search for new target molecules for chemotherapy.