p27 as Jekyll and Hyde: regulation of cell cycle and cell motility.
p27 is a key regulator of cell proliferation. While it opposes cell cycle progression by binding to and inhibiting cyclin E-Cdk2, T157/T198 phosphorylation of p27 promotes its assembly of D-type cyclin-CDKs. In addition to its actions on the cell cycle, p27 regulates CDK-independent cytoplasmic functions. In human cancers, oncogenic activation of the PI3K signaling pathway often results in cytoplasmic mislocalization of p27. Cytoplasmic p27 plays an important role in cell motility and migration; it binds RhoA and modulates activation of the RhoA/ROCK cascade. p27:RhoA binding is facilitated by p27 phosphorylation at threonine 198. Accumulation of cytoplasmic p27 leads to increased cellular motility, a critical event in tumor metastasis. Further characterization of post-translational modifications governing p27 localization and its action on RhoA and the actin cytoskeleton may provide critical insights into human cancer metastasis.
Larrea
Michelle D
MD
Braman Family Breast Cancer Institute, University of Miami Sylvester Comprehensive Cancer Center and Department of Biochemistry and Molecular Biology, UM Miller School of Medicine, Miami, FL, USA.
Wander
Seth A
SA
Slingerland
Joyce M
JM
D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
C109198:CIB1 protein, human; D002135:Calcium-Binding Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D011494:Protein Kinases; D018844:Cyclin-Dependent Kinases