SCIENCE@home

Protein Kinase Cδ Stimulates Proteasome-Dependent Degradation of C/EBPα during Apoptosis Induction of Leukemic Cells

Meng Zhao,Xu-Fang Duan,Xu-Yun Zhao,Bo Zhang,Ying Lu,Wei Liu,Jin Cheng,Guoqiang Chen

Published 2009 in PLoS ONE

ABSTRACT

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/EBPα) 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/EBPα protein during apoptosis induction. Methodology/Principal Findings Upon onset of apoptosis induced by various kinds of inducers such as NSC606985, etoposide and others, C/EBPα 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 (PKCδ), which was proteolytically activated during apoptosis induction tested, we showed that the active PKCδ protein contributed to the increased degradation of C/EBPα protein. Three specific proteasome inhibitors antagonized C/EBPα degradation during apoptosis induction. More importantly, ectopic expression of PKCδ-CF stimulated the ubiquitination of C/EBPα protein, while the chemical inhibition of PKCδ action significantly inhibited the enhanced ubiquitination of C/EBPα protein under NSC606985 treatment. Additionally, silencing of C/EBPα expression by small interfering RNAs enhanced, while inducible expression of C/EBPα inhibited NSC606985/etoposide-induced apoptosis in leukemic cells. Conclusions/Significance These observations indicate that the activation of PKCδ upon apoptosis results in the increased proteasome-dependent degradation of C/EBPα, which partially contributes to PKCδ-mediated apoptosis.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-78 of 78 references · Page 1 of 1

CITED BY

Showing 1-13 of 13 citing papers · Page 1 of 1