The function of p27 KIP1 during tumor development.
Timely cell cycle regulation is conducted by sequential activation of a family of serine-threonine kinases called cycle dependent kinases (CDKs). Tight CDK regulation involves cyclin dependent kinase inhibitors (CKIs) which ensure the correct timing of CDK activation in different phases of the cell cycle. One CKI of importance is p27(KIP1). The regulation and cellular localization of p27(KIP1) can result in biologically contradicting roles when found in the nucleus or cytoplasm of both normal and tumor cells. The p27(KIP1) protein is mainly regulated by proteasomal degradation and its downregulation is often correlated with poor prognosis in several types of human cancers. The protein can also be functionally inactivated by cytoplasmic localization or by phosphorylation. The p27(KIP1) protein is an unconventional tumor suppressor because mutation of its gene is extremely rare in tumors, implying the normal function of the protein is deranged during tumor development. While the tumor suppressor function is mediated by p27(KIP1)s inhibitory interactions with the cyclin/CDK complexes, its oncogenic function is cyclin/CDK independent, and in many cases correlates with cytoplasmic localization. Here we review the basic features and novel aspects of the p27(KIP1) protein, which displays genetically separable tumor suppressing and oncogenic functions.
Lee
Jinhwa
J
Department of Clinical Lab Science, Dongseo University, Busan 617-716, Korea.
Kim
Sung Soo
SS
D000818:Animals; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases