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Comment
. 2003 Dec 23;100(26):15290-1.
doi: 10.1073/pnas.0307282100. Epub 2003 Dec 15.

Another twist in the transforming growth factor beta-induced cell-cycle arrest chronicle

Catherine Denicourt  1 , Steven F Dowdy
Affiliations
Comment

Another twist in the transforming growth factor beta-induced cell-cycle arrest chronicle

Catherine Denicourt et al. Proc Natl Acad Sci U S A. .
No abstract available

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Figures

Fig. 1.
Fig. 1.
TGF-β signaling pathway. TGF-β binding to the type II receptor results in phosphorylation and activation of the type I receptor. The activated type I receptor then phosphorylates the receptor-associated SMADs (SMAD 2/3) that promote dimer or trimer formation with SMAD4 followed by nuclear translocation. SMAD complexes, in collaboration with cofactors, modulate transcription of TGF-β target genes. Induction of cell-cycle arrest by TGF-β involves transcription of CDK inhibitors p15INK4b and p21CIP1. p15INK4b specifically inhibits CDK4/6, whereas p21CIP1 inhibits cyclin E–CDK2 complexes. The inhibited cyclin–CDK complexes can drive progression of the cell cycle for a longer time. Activation of CDK2 requires phosphorylation of its Thr-160 residue by CAK and removal of inhibitory phosphates on Thr-14 and Tyr-15 by Cdc25A phosphatase. The new pathway proposed by Bhowmick et al. (6) involves TGF-β activation of the RhoA/p160ROCK signaling pathway. By an undefined mechanism, TGF-β activates RhoA and causes the translocation of p160ROCK to the nucleus, where it phosphorylates and inactivates Cdc25A and thereby prevents activation of CDK2.
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