RhoA signaling in phorbol ester-induced apoptosis |
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Authors: | Zee-Fen Chang Hsiao-Hui Lee |
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Institution: | (1) Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei, Taiwan, ROC |
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Abstract: | Summary Exposure of cells to phorbol ester activates protein kinase C (PKC) to induce apoptosis or differentiation, depending on the
cellular context. In erythroblastic cell lines, TF-1 and D2, upregulation of the RhoA signaling promotes phorbol ester-induced
apoptosis through activating Rho-associated kinase (ROCK)/phosphorylation of myosin light chain (MLC), thus generating membrane
contraction force. As a result, cell adhesion is inhibited and death receptor-mediated death pathway is activated in these
cells with a concurrent changes in nucleocytoplasmic signaling for protein trafficking. A microtubule-regulated GEF-H1, which
is a specific RhoA activator, was identified to contribute to RhoA activation in these cells. Thus, a cytoskeleton-regulated
RhoA signaling cooperates with PKC activation constitutes a cellular context to determine the cell fate in response to phorbol
ester stimulation. |
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Keywords: | apoptosis phorbol ester Rho A |
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