2. Academic Validation
  3. C/EBPbeta phosphorylation by RSK creates a functional XEXD caspase inhibitory box critical for cell survival

C/EBPbeta phosphorylation by RSK creates a functional XEXD caspase inhibitory box critical for cell survival

  • Mol Cell. 2001 Oct;8(4):807-16. doi: 10.1016/s1097-2765(01)00374-4.
M Buck 1,  V Poli,  T Hunter,  M Chojkier
Affiliations

Affiliation

  • 1 Molecular Biology and Virology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
PMID: 11684016 DOI: 10.1016/s1097-2765(01)00374-4
Abstract

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).

Figures