Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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The function of $p27^{KIP1}$ during tumor development

Lee, Jin-Hwa;Kim, Sung-Soo

  • Published : 20091100
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Abstract

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.

Keywords

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