TGFbeta prevents proteasomal degradation of the cyclin-dependent kinase inhibitor p27kip1 for cell cycle arrest.

TGFbeta mediates cell cycle arrest in late G(1) phase of the cell cycle with a simultaneous peak in the levels of the cyclin-dependent kinase inhibitor, p27(kip1) (p27). In this report, we show that whereas p27 resides in the cytoplasm in the endometrial carcinoma (ECA) cell line HEC-1A, TGFbeta increases the total levels and translocation of p27 into the nucleus. Concomitantly, TGFbeta activates the transcription factors Smad2 and Smad3, inhibits proliferation, and blocks Cdk2 activity; all these events are blocked by an inhibitor of TbetaRI serine kinase activity (SD208).