The Role of Cell Cycle Regulators in Normal and Malignant Cell Proliferation

Cell proliferation is governed by precise and orderly process the regulation of which involves many different proteins. The key enzyme for cell growth and arrest is cyclin dependent kinases (cdks). In human cells, several cdks orchestrate four distinct cell cycle phases (M, G₁, S and G₂) and they sequentially operate in an order of cdc1, cdk4, cdk6 and cdk2. The regulatory components of cdks consist of cyclins and two family of cdk inhibitors, INK4 (inhibitors of cdk4) and KIP (kinase inhibitor protein). G1 regulatory molecules for cdk mainly respond to environmental cues of mitogenic and anti-mitogenic stimuli and therefore influence activities of G1 cdks, namely, cdk4/6 and cdk2. G₁ inhibitors include p21 CIP and p27 KIP1 . Between them, p27 KIP1 has attracted attentions of many researchers because of its characteristic regulatory features and diverse functions. Besides, the role of p27 KIP1 in cancer development warrants further studies in the future. Therefore, this review will focus on the recent findings and especially on the complexity of regulatory mechanisms of p27 KIP1 .