Transforming growth factor β effects on expression of G1 cyclins and cyclin-dependent protein kinases

Abstract

Transforming growth factor β1 (TGF-β1) is a potent growth-inhibitory polypeptide. The mechanism of TGF-β1 inhibition has been related to its ability to prevent the hyperphosphorylation of retinoblastoma protein (pRb). Several lines of evidence have suggested that cell cycle-regulated protein kinases are responsible for the hyperphosphorylation of pRb We demonstrate here that TGF-β1 has profound effects on the expression of genes encoding certain G1 cyclins and their associated kinases, which provides one explanation of TGF-β1 effects on pRb hyperphosphorylation. These results also suggest that the growth-inhibitory effects of TGF-β1 in many cells are attributable to its effects on the cell cycle apparatus involved in programming G1 transit.