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Inhibition of G1 phase cyclin dependent kinases by transforming growth factor β1
Author(s) -
Reddy Kumar B.,
Hocevar Barbara A.,
Howe Philip H.
Publication year - 1994
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240560318
Subject(s) - cyclin a , cyclin d , microbiology and biotechnology , cyclin dependent kinase 2 , cyclin dependent kinase , cyclin e , cell cycle , cyclin b , cyclin a2 , cyclin dependent kinase complex , transforming growth factor , cyclin dependent kinase 3 , chemistry , cyclin , cancer research , kinase , biology , protein kinase a , cell , biochemistry
Transforming growth factor β1 (TGFβ1) inhibits epithelial cell proliferation late in the G1 phase of the cell cycle. We examined the effect of TGFβ1 on known late G1 cell cycle regulators in an attempt to determine the molecular mechanism of growth inhibition by this physiological inhibitor. The results demonstrate the TGFβ1 inhibits the late G1 and S phase specific histone H1 kinase activity of p33 cdk2 . This inhibitiion is not dur to TGFβ1's effect on p33 cdk2 synthesis, but rather due to its negative effect on the late G1 phosphorylation of p33 cdk2 . It is also shown that TGFβ1 inhibits both late G1 cyclin A and cyclin E associated histon H1 kinase activities. The inhibitor has no effects on the synthesis of cyclin E but to inhibit the synthesis of cyclin A protein in a cell cycle dependent manner. If TGFβ1 is added to cells which have progressed futher than 8 hours into G1, then it is without inhibitory effect on cyclin A synthesis. These effect on TGFβ1 on late G1 cell cycle regulators correlate well with its inhibitory effects on cellular growth and suggest that these G1 cyclin dependent kinases might serve as targets for TGFβ1‐mediated growth arrest.