| First Author | Buck M | Year | 2001 |
| Journal | Mol Cell | Volume | 8 |
| Issue | 4 | Pages | 807-16 |
| PubMed ID | 11684016 | Mgi Jnum | J:72719 |
| Mgi Id | MGI:2153436 | Doi | 10.1016/s1097-2765(01)00374-4 |
| Citation | Buck M, et al. (2001) C/EBPbeta Phosphorylation by RSK Creates a Functional XEXD Caspase Inhibitory Box Critical for Cell Survival. Mol Cell 8(4):807-16 |
| 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). |
