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Protein kinase C-delta mediates down-regulation of heterogeneous nuclear ribonucleoprotein K protein: involvement in apoptosis induction.
- Source :
-
Experimental cell research [Exp Cell Res] 2009 Nov 15; Vol. 315 (19), pp. 3250-8. Date of Electronic Publication: 2009 Sep 10. - Publication Year :
- 2009
-
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.
Details
- Language :
- English
- ISSN :
- 1090-2422
- Volume :
- 315
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Experimental cell research
- Publication Type :
- Academic Journal
- Accession number :
- 19747914
- Full Text :
- https://doi.org/10.1016/j.yexcr.2009.09.005