C/EBPβ Phosphorylation by RSK Creates a Functional XEXD Caspase Inhibitory Box Critical for Cell Survival
2001; Elsevier BV; Volume: 8; Issue: 4 Linguagem: Inglês
10.1016/s1097-2765(01)00374-4
ISSN1097-4164
AutoresMartina Buck, Valeria Poli, Tony Hunter, Mario Chojkier,
Tópico(s)Cancer-related Molecular Pathways
ResumoAbstract 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/EBPβ on Thr 217 , and proliferation of stellate cells in normal mice, but caused apoptosis of these cells in C/EBPβ −/− or C/EBPβ-Ala 217 (a dominant-negative nonphosphorylatable mutant) transgenic mice. Both C/EBPβ-PThr 217 and the phosphorylation mimic C/EBPβ-Glu 217 , but not C/EBPβ-Ala 217 , were associated with procaspases 1 and 8 in vivo and in vitro and inhibited their activation. Our data suggest that C/EBPβ phosphorylation on Thr 217 creates a functional XEXD caspase substrate/inhibitor box (K-Phospho-T 217 VD) that is mimicked by C/EBPβ-Glu 217 (KE 217 VD). C/EBPβ −/− and C/EBPβ - Ala 217 stellate cells were rescued from apoptosis by the cell permeant KE 217 VD tetrapeptide or C/EBPβ-Glu 217 .
Referência(s)