Phorbol 12-myristate 13-acetate promotes nuclear translocation of hepatic steroid response element binding protein-2
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香港中文大學研究人員

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摘要Sterol regulatory element-binding protein (SREBP)-2 is a pivotal transcriptional factor in cholesterol metabolism. Factors interfering with the proper functioning of SREBP-2 potentially alter plasma lipid profiles. Phorbol 12-myristate 13-acetate (PMA), which is a common protein kinase C (PKC) activator, was shown to promote the post-translational processing and nuclear translocation of SREBP-2 in hepatic cells in the current study. Following SREBP-2 translocation, the transcripts of its target genes HMGCR and LDLR were upregulated as demonstrated by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Electrophoretic mobility shift assays (EMSA) also demonstrated an induced DNA-binding activity on the sterol response element (SRE) domain under PMA treatment. The increase of activated Srebp-2 without the concurrent induced mRNA expression was also observed in an animal model. As the expression of SREBP-2 was not increased by PMA, the activation of PKC was the focus of investigation. Specific PKC isozyme inhibition and overexpression supported that PKC beta was responsible for the promoting effect. Further studies showed that the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinases (JNK), but not 5' adenosine monophosphate-activated protein kinase (AMPK), were the possible downstream signaling proteins of PKC beta. In conclusion, this study illustrated that PKC beta increased SREBP-2 nuclear translocation in a pathway mediated by MEK/ERK and JNK, rather than the one dictated by AMPK. These results revealed a novel signaling target of PKC beta in the liver cells. (C) 2016 Elsevier Ltd. All rights reserved.
著者Wong TY, Tan YQ, Lin SM, Leung LK
期刊名稱International Journal of Biochemistry and Cell Biology
出版年份2016
月份6
日期1
卷號75
出版社PERGAMON-ELSEVIER SCIENCE LTD
頁次1 - 10
國際標準期刊號1357-2725
電子國際標準期刊號1878-5875
語言英式英語
關鍵詞Liver; Phorbol ester; PKC; SREBP-2
Web of Science 學科類別Biochemistry & Molecular Biology; Cell Biology

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