Chemistry and Physics Faculty Articles

Title

p27 as Jekyll and Hyde: Regulation of Cell Cycle and Cell Motility

Document Type

Article

Publication Date

11-2009

Publication Title

Cell Cycle

Keywords

Cell cycle, CDK inhibition, p27, RhoA, Cell motility, Metastasis, Phosphorylation, PI3K, PKB, mTOR, SGK, RSK

ISSN

1538-4101

Volume

8

Issue/No.

21

First Page

3455

Last Page

3461

Abstract

p27 is a key regulator of cell proliferation. While it opposes cell cycle progression by binding to and inhibiting cyclin E-Cdk2, T157/198 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 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.

Comments

©2009 Landes Bioscience

Additional Comments

NCI grant #: 1R01CA105118-01

DOI

10.4161/cc.8.21.9789