Regulation of apoptotic and growth inhibitory activities of C/EBPα in different cell lines

C/EBP(x is expressed in many tissues and inhibits cell growth. in this paper, we have examined mechanisms which regulate activities of C/EBP alpha in cell lines derived from different tissues. We found that C/EBP alpha possesses strong pro-apoptotic activity in NIH3T3 cells, while this activity is not detected in 3T3-L1, Hep3B2 and HEK293 cells. Micro-array data show that C/EBP alpha activates many genes of apoptosis signaling in NIH3T3 cells. one of these genes, ARL6IP5, is a direct target of C/EBP alpha and is a key mediator of the apoptosis. Using C/EBP alpha mutants which do not cause cell death; we have found that C/EBP alpha does not arrest proliferation of NIH3T3 cells. The lack of growth arrest in NIH3T3 cells correlates with the inhibition of p16INK4 and with low levels of cyclin D3. The limited growth inhibitory activity of C/EBP alpha is also observed in Hep3B2 cells which express low levels of cyclin D3. Elevation of cyclin D3 restores growth inhibitory activity of C/EBP alpha in NIH3T3 and in Hep3B2 cells. These data show that apoptotic and growth inhibitory activities of C/EBP alpha are differentially regulated in different cells and that cooperation of cyclin D3 and C/EBP alpha is required for the inhibition of proliferation. (C) 2008 Elsevier Inc. All rights reserved.