title: p27Kip1 inhibits the cell cycle through non-canonical G1/S phase-specific gatekeeper mechanism.
abstract: The cyclin-dependent kinase (CDK) inhibitor p27Kip1 has been shown to regulate cellular proliferation via inhibition of CDK activities. It is now recognized that p27Kip1 can regulate cellular processes through non-canonical, CDK-independent mechanisms. We have developed an inducible p27Kip1 model in cultured cells to explore CDK-independent p27Kip1 regulation of biological processes. We present evidence that p27Kip1 can function in a CDK-independent manner to inhibit entry and/or progression of S phase. Even though this p27Kip1 mechanism is non-canonical it does requires the intact cyclin-binding motif in p27Kip1. We suggest a mechanism similar to that proposed in post-mitotic neural cells whereby p27Kip1 functions to coordinate growth arrest and apoptosis. Our hypothesis supports the concept that p27Kip1 is a gatekeeper for the entry and progression of S phase through interaction with specific protein(s) or via binding to specific DNA sequences in a CDK-independent manner.
authors.affiliation: a Gibbs Cancer Center and Research Institute ; Spartanburg , SC.
authors.forename: Savitha S
authors.initials: SS
authors.lastname: Sharma
authors.affiliation: a Gibbs Cancer Center and Research Institute ; Spartanburg , SC.
authors.forename: Le
authors.initials: L
authors.lastname: Ma
authors.affiliation: a Gibbs Cancer Center and Research Institute ; Spartanburg , SC.|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: D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase / Q000235:genetics*; D006801:Humans; D015739:Nocodazole / Q000494:pharmacology; D016196:S Phase / Q000235:genetics*
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27; D015739:Nocodazole
keywords: cell cycle; cyclin F; cyclin-dependent kinases; non-canonical; p27Kip1