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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Robert A. Weinberg (1993) studied this question.
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