title: The non-canonical functions of p27(Kip1) in normal and tumor biology.
abstract: p27(Kip1) was first discovered as a key regulator of cell proliferation. The canonical function of p27(Kip1) is inhibition of cyclin-dependent kinase (CDK) activity. In addition to its initial identification as a CDK inhibitor, p27(Kip1) has also emerged as an intrinsically unstructured, multifunctional protein with numerous non-canonical, CDK-independent functions that exert influence on key processes such as cell cycle regulation, cytoskeletal dynamics and cellular plasticity, cell migration, and stem-cell proliferation and differentiation. Many of these non-canonical functions, depending on the cell-specific contexts such as oncogenic activation of signaling pathways, have the ability to turn pro-oncogenic in nature and even contribute to tumor-aggressiveness and metastasis. This review discusses the various non-canonical, CDK-independent mechanisms by which p27(Kip1) functions either as a tumor-suppressor or tumor-promoter.
authors.affiliation: a Gibbs Cancer Center & Research Institute , Spartanburg , SC , USA.
authors.forename: Savitha S
authors.initials: SS
authors.lastname: Sharma
authors.affiliation: a Gibbs Cancer Center & Research Institute , Spartanburg , SC , USA.|b Edward Via College of Osteopathic Medicine , Department of Molecular Medicine , Spartanburg , SC , USA.
authors.forename: W Jackson
authors.initials: WJ
authors.lastname: Pledger
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002465:Cell Movement; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D013234:Stem Cells / Q000378:metabolism
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: cell cycle; cell migration; cyclin-dependent kinases; metastasis; non-canonical functions; p27Kip1; stem-cell biology