Protein kinase C-delta mediates down-regulation of heterogeneous nuclear ribonucleoprotein K protein: involvement in apoptosis induction.

Abstract

We reported previously that NSC606985, a camptothecin analogue, induces apoptosis of acute myeloid leukemia (AML) cells through proteolytic activation of protein kinase C delta (DeltaPKC-delta). By subcellular proteome analysis, heterogeneous nuclear ribonucleoprotein K (hnRNP K) was identified as being significantly down-regulated in NSC606985-treated leukemic NB4 cells. HnRNP K, a docking protein for DNA, RNA, and transcriptional or translational molecules, is implicated in a host of processes involving the regulation of gene expression. However, the molecular mechanisms of hnRNP K reduction and its roles during apoptosis are still not understood. In the present study, we found that, following the appearance of the DeltaPKC-delta, hnRNP K protein was significantly down-regulated in NSC606985, doxorubicin, arsenic trioxide and ultraviolet-induced apoptosis. We further provided evidence that DeltaPKC-delta mediated the down-regulation of hnRNP K protein during apoptosis: PKC-delta inhibitor could rescue the reduction of hnRNP K; hnRNP K failed to be decreased in PKC-delta-deficient apoptotic KG1a cells; conditional induction of DeltaPKC-delta in U937T cells directly down-regulated hnRNP K protein. Moreover, the proteasome inhibitor also inhibited the down-regulation of hnRNP K protein by apoptosis inducer and the conditional expression of DeltaPKC-delta. More intriguingly, the suppression of hnRNP K with siRNA transfection significantly induced apoptosis. To our knowledge, this is the first demonstration that proteolytically activated PKC-delta down-regulates hnRNP K protein in a proteasome-dependent manner, which plays an important role in apoptosis induction.

• Authors: Feng-Hou Gao, Ying-Li Wu, Meng Zhao, Chuan-Xu Liu, Li-Shun Wang, Guo-Qiang Chen
• Journal: Experimental cell research (Exp Cell Res) Vol. 315 Issue 19 Pg. 3250-8 (Nov 15 2009) ISSN: 1090-2422 [Electronic] United States
• PMID: 19747914 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Heterogeneous-Nuclear Ribonucleoprotein K
• Protein Kinase C-delta
• Proteasome Endopeptidase Complex

Topics

• Apoptosis
• Cell Line, Tumor
• Down-Regulation (genetics)
• Heterogeneous-Nuclear Ribonucleoprotein K (genetics)
• Humans
• Leukemia, Myeloid, Acute (metabolism, pathology)
• Proteasome Endopeptidase Complex
• Protein Kinase C-delta (physiology)