Transforming growth factor beta effects on expression of G1 cyclins and cyclin-dependent protein kinases.
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.
Geng
Y
Y
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142.
Weinberg
R A
RA
D015152:Blotting, Northern; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D016213:Cyclins / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D011494:Protein Kinases / Q000096:biosynthesis*; D012313:RNA / Q000302:isolation & purification / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016213:Cyclins; D016212:Transforming Growth Factor beta; D012313:RNA; D011494:Protein Kinases