Our previous study has shown that PKC delta stimulates proteasome-dependent degradation of C/EBP alpha, which partially contributes to PKC delta-mediated apoptosis. However, the molecular interrelationship between these two important proteins is still unknown. In this study, we reported that C/EBP alpha was phosphorylated by activated PKC delta on three serines, two of which were reported for the first time. Phosphorylated C/EBP alpha underwent cytoplasmic translocation, which led to the inactivation of its transcriptional activity. Inactive cytoplasmic C/EBP alpha was finally subjected to proteasome degradation. This work reveals the exquisite molecular events linking activated PKC delta and C/EBP alpha degradation during cell apoptosis. (C) 2013 Elsevier Inc. All rights reserved.