p27Kip1 inhibits the cell cycle through non-canonical G1/S phase-specific gatekeeper mechanism |
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Authors: | Savitha S Sharma Le Ma W Jackson Pledger |
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Institution: | 1.Gibbs Cancer Center and Research Institute; Spartanburg, SC;2.Edward Via College of Osteopathic Medicine; Department of Molecular Medicine; Spartanburg, SC USA |
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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. |
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Keywords: | cell cycle p27Kip1 non-canonical cyclin-dependent kinases cyclin F |
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