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rdf:type |
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lifeskim:mentions |
umls-concept:C0007620,
umls-concept:C0010656,
umls-concept:C0021469,
umls-concept:C0031715,
umls-concept:C0179400,
umls-concept:C0205245,
umls-concept:C1419742,
umls-concept:C1419743,
umls-concept:C1419744,
umls-concept:C1511545,
umls-concept:C1706214
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pubmed:issue |
4
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pubmed:dateCreated |
2001-10-30
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pubmed:abstractText |
Upon 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).
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
807-16
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11684016-Acetylcysteine,
pubmed-meshheading:11684016-Amino Acid Motifs,
pubmed-meshheading:11684016-Animals,
pubmed-meshheading:11684016-Apoptosis,
pubmed-meshheading:11684016-CCAAT-Enhancer-Binding Protein-beta,
pubmed-meshheading:11684016-Carbon Tetrachloride,
pubmed-meshheading:11684016-Caspases,
pubmed-meshheading:11684016-Cell Survival,
pubmed-meshheading:11684016-Cells, Cultured,
pubmed-meshheading:11684016-Culture Media, Serum-Free,
pubmed-meshheading:11684016-Enzyme Activation,
pubmed-meshheading:11684016-Enzyme Precursors,
pubmed-meshheading:11684016-Hepatocytes,
pubmed-meshheading:11684016-Humans,
pubmed-meshheading:11684016-Liver Cirrhosis, Experimental,
pubmed-meshheading:11684016-Male,
pubmed-meshheading:11684016-Mice,
pubmed-meshheading:11684016-Mice, Transgenic,
pubmed-meshheading:11684016-Microscopy, Confocal,
pubmed-meshheading:11684016-Phosphorylation,
pubmed-meshheading:11684016-Rats,
pubmed-meshheading:11684016-Recombinant Proteins,
pubmed-meshheading:11684016-Ribosomal Protein S6 Kinases
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pubmed:year |
2001
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pubmed:articleTitle |
C/EBPbeta phosphorylation by RSK creates a functional XEXD caspase inhibitory box critical for cell survival.
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pubmed:affiliation |
Molecular Biology and Virology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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