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Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10315-9.

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

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  • 1Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.


Transforming growth factor beta 1 (TGF-beta 1) is a potent growth-inhibitory polypeptide. The mechanism of TGF-beta 1 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-beta 1 has profound effects on the expression of genes encoding certain G1 cyclins and their associated kinases, which provides one explanation of TGF-beta 1 effects on pRb hyperphosphorylation. These results also suggest that the growth-inhibitory effects of TGF-beta 1 in many cells are attributable to its effects on the cell cycle apparatus involved in programming G1 transit.

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