%0 Journal Article
%T Protein Kinase C¦Ä Stimulates Proteasome-Dependent Degradation of C/EBP¦Á during Apoptosis Induction of Leukemic Cells
%A Meng Zhao
%A Xu-Fang Duan
%A Xu-Yun Zhao
%A Bo Zhang
%A Ying Lu
%A Wei Liu
%A Jin-Ke Cheng
%A Guo-Qiang Chen
%J PLOS ONE
%D 2009
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0006552
%X Background The precise regulation and maintenance of balance between cell proliferation, differentiation and death in metazoan are critical for tissue homeostasis. CCAAT/enhancer-binding protein alpha (C/EBP¦Á) has been implicated as a key regulator of differentiation and proliferation in various cell types. Here we investigated the potential dynamic change and role of C/EBP¦Á protein during apoptosis induction. Methodology/Principal Findings Upon onset of apoptosis induced by various kinds of inducers such as NSC606985, etoposide and others, C/EBP¦Á expression presented a profound down-regulation in leukemic cell lines and primary cells via induction of protein degradation and inhibition of transcription, as assessed respectively by cycloheximide inhibition test, real-time quantitative RT-PCR and luciferase reporter assay. Applying chemical inhibition, forced expression of dominant negative mutant and catalytic fragment (CF) of protein kinase Cdelta (PKC¦Ä), which was proteolytically activated during apoptosis induction tested, we showed that the active PKC¦Ä protein contributed to the increased degradation of C/EBP¦Á protein. Three specific proteasome inhibitors antagonized C/EBP¦Á degradation during apoptosis induction. More importantly, ectopic expression of PKC¦Ä-CF stimulated the ubiquitination of C/EBP¦Á protein, while the chemical inhibition of PKC¦Ä action significantly inhibited the enhanced ubiquitination of C/EBP¦Á protein under NSC606985 treatment. Additionally, silencing of C/EBP¦Á expression by small interfering RNAs enhanced, while inducible expression of C/EBP¦Á inhibited NSC606985/etoposide-induced apoptosis in leukemic cells. Conclusions/Significance These observations indicate that the activation of PKC¦Ä upon apoptosis results in the increased proteasome-dependent degradation of C/EBP¦Á, which partially contributes to PKC¦Ä-mediated apoptosis.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0006552