The non-canonical functions of p27Kip1 in normal and tumor biology |
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Authors: | Savitha S Sharma |
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Institution: | 1. Gibbs Cancer Center &2. Research Institute, Spartanburg, SC, USA |
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Abstract: | p27Kip1 was first discovered as a key regulator of cell proliferation. The canonical function of p27Kip1 is inhibition of cyclin-dependent kinase (CDK) activity. In addition to its initial identification as a CDK inhibitor, p27Kip1 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 p27Kip1 functions either as a tumor-suppressor or tumor-promoter. |
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Keywords: | cell cycle cell migration cyclin-dependent kinases metastasis non-canonical functions p27Kip1 stem-cell biology |
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