Linked Life Data

11684016

Source:http://linkedlifedata.com/resource/pubmed/id/11684016

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pubmed-article:11684016pubmed:abstractTextUpon activation by liver injury, hepatic stellate cells produce excessive fibrous tissue leading to cirrhosis. The hepatotoxin CCl(4) induced activation of RSK, phosphorylation of C/EBPbeta on Thr(217), and proliferation of stellate cells in normal mice, but caused apoptosis of these cells in C/EBPbeta-/- or C/EBPbeta-Ala(217) (a dominant-negative nonphosphorylatable mutant) transgenic mice. Both C/EBPbeta-PThr(217) and the phosphorylation mimic C/EBPbeta-Glu(217), but not C/EBPbeta-Ala(217), were associated with procaspases 1 and 8 in vivo and in vitro and inhibited their activation. Our data suggest that C/EBPbeta phosphorylation on Thr(217) creates a functional XEXD caspase substrate/inhibitor box (K-Phospho-T(217)VD) that is mimicked by C/EBPbeta-Glu(217) (KE(217)VD). C/EBPbeta-/- and C/EBPbeta-Ala(217) stellate cells were rescued from apoptosis by the cell permeant KE(217)VD tetrapeptide or C/EBPbeta-Glu(217).lld:pubmed
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pubmed-article:11684016pubmed:articleTitleC/EBPbeta phosphorylation by RSK creates a functional XEXD caspase inhibitory box critical for cell survival.lld:pubmed
pubmed-article:11684016pubmed:affiliationMolecular Biology and Virology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.lld:pubmed
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