Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclin-dependent kinases (cdks) are a family of proteins whose function plays a critical role in cell cycle traverse. Transforming growth factor-beta 1 (TGF-beta 1) is a potent growth inhibitor of epithelial cells. Since cdks have been suggested as possible biochemical markers for TGF-beta growth inhibition, we investigated the effect of TGF-beta 1 on cdc2 and cdk2 in a normal mouse mammary epithelial cell line (MME) and a TGF-beta-resistant MME cell line (BG18.2). TGF-beta 1 decreases newly synthesized cdc2 protein levels within 6 h after addition. Coincident with this decrease in newly synthesized cdc2 protein was a marked reduction in its ability to phosphorylate histone H1. This decrease in kinase activity is not due to a change in steady-state levels of cdc2 protein, since mRNA and total protein levels of cdc2 are not reduced until 12 h after TGF-beta 1 addition. This suggests that the kinase activity of cdc2 is dependent on newly synthesized cdc2 protein. Moreover, the protein synthesis of another cyclin-dependent kinase, cdk2, is not effected by TGF-beta 1 addition, but its kinase activity is substantially reduced. Thus, it appears that TGF-beta decreases the kinase activity of both cdc2 and cdk2 by distinct mechanisms.
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PMID:Differential regulation of p34cdc2 and p33cdk2 by transforming growth factor-beta 1 in murine mammary epithelial cells. 759 74

Type beta transforming growth factors represent a family of polypeptides that modulate growth and differentiation. They exert their effect on target cells through interaction with multiple cell surface receptors. Transforming growth factor-beta 1 has a strong inhibitory action on cell division in mink lung CC164 cells, a process that is initiated by immediate induction of junB and phosphorylation of nuclear protein followed by a reduced expression of cdk4. However, its signal transduction pathways are still unresolved. In this study we report a detailed analysis of cell kinetic events following addition of transforming growth factor-beta 1 to mink lung CCL64 cells. We show that transforming growth factor-beta 1 reduces [3H]thymidine incorporation after a delay of 8 hours, which reaches its nadir at 16 hours. The reduced growth rate is maintained for at least 48 hours as shown by flow cytometric analysis of DNA content. Using time-lapse video microscopy it was shown that control cells double on average every 14.4 hours, whereas the transforming growth factor-beta 1-treated cells have a doubling time of on average 20.3 hours. The difference in intermitotic time is a consequence of a prolonged G1 phase (a shift from 7.5 to 13.5 hours on average). However, changes in intermitotic times occur only after cells have undergone division in the presence of transforming growth factor-beta 1 and treated cells finish the ongoing cell cycle exactly like control cells. From these findings we conclude that transforming growth factor-beta 1 may change cell cycle parameters by interfering with cellular events prior to G1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Initiation of growth inhibition by TGF beta 1 is unlikely to occur in G1. 770 98

Transforming growth factor-beta 1 (TGF-beta 1) inhibits the growth of intestinal cells, but the mechanisms involved are unknown. Using a rat intestinal crypt cell line (IEC-6), we determined the site of action in the cell cycle that TGF-beta 1 acts to suppress proliferation. We also examined the effect of TGF-beta 1 on the expression of proliferation-associated "immediate early" genes (zif268, jun-B, c-myc) during the early G1 phase and the cdc2 gene during the transition from the G1 phase to the S phase of the cell cycle. Cell cycle progression was determined by incorporation of 3H-thymidine, and gene expression was analyzed by Northern blot analysis. We found that TGF-beta 1 acts to inhibit proliferation of rat intestinal crypt cells by blocking cell cycle progression at the middle G1 phase. The genes activated during G1 can be divided into TGF-beta 1 insensitive (zif268, jun-B, and c-myc) and TGF-beta 1 sensitive (the cdc2 gene). TGF-beta 1 suppresses the induction of the cdc2 gene during the G1/S transition without inhibiting the activation of immediate early genes during the early G1 phase.
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PMID:Transforming growth factor-beta inhibits rat intestinal cell growth by regulating cell cycle specific gene expression. 831 Nov 25