期刊
EXPERIMENTAL CELL RESEARCH
卷 315, 期 19, 页码 3250-3258出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2009.09.005
关键词
hnRNP K; PKC-delta; Proteasome; Apoptosis
资金
- National Natural Science Foundation [30630034, 30870523]
- Ministry of Science and Technology [N02009CB918400]
- National 973 Program of China [N02002CB512805]
- Chinese Academy of Sciences [KSCX2-YW-R-097]
- National 863 Program [2006AA02Z105]
- Science and Technology Committee of Shanghai [08JC1413400]
- Education Committee Project of Shanghai [08YZ45]
- Shanghai Ling-Jun Talent Program
We reported previously that NSC606985, a camptothecin analogue, induces apoptosis of acute myeloid leukemia (AML) cells through proteolytic activation of protein kinase C delta (Delta PKC-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 Delta PKC-delta, hnRNP K protein was significantly down-regulated in NSC606985, doxorubicin, arsenic trioxide and ultraviolet-induced apoptosis. We further provided evidence that Delta PKC-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 Delta PKC-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 Delta PKC-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. (C) 2009 Published by Elsevier Inc.
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