Secretogranin II: a key AP-1-regulated protein that mediates neuronal differentiation and protection from nitric oxide-induced apoptosis of neuroblastoma cells

被引：0
作者：
L Li
A C Hung
A G Porter
机构：
[1] Cell Death and Human Disease Group,Division of Cancer and Developmental Cell Biology
[2] Institute of Molecular and Cell Biology,undefined
[3] A*STAR (Agency for Science,undefined
[4] Technology and Research),undefined
来源：
Cell Death & Differentiation | 2008年 / 15卷
关键词：
nitric oxide; apoptosis; AP-1; secretogranin; neuronal differentiation;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Identification of AP-1 target genes in apoptosis and differentiation has proved elusive. Secretogranin II (SgII) is a protein widely distributed in nervous and endocrine tissues, and abundant in neuroendocrine granules. We addressed whether SgII is regulated by AP-1, and if SgII is involved in neuronal differentiation or the cellular response to nitrosative stress. Nitric oxide (NO) upregulated sgII mRNA dependent on a cyclic AMP response element (CRE) in the sgII promoter, and NO stimulated SgII protein secretion in neuroblastoma cells. Upregulation of sgII mRNA, sgII CRE-driven gene expression and SgII protein synthesis/export were attenuated in cells transformed with dominant-negative c-Jun (TAM67), which became sensitized to NO-induced apoptosis and failed to undergo nerve growth factor-dependent neuronal differentiation. Stable transformation of TAM67 cells with sgII restored neuronal differentiation and resistance to NO. RNAi knockdown of sgII in cells expressing functional c-Jun abolished neuronal differentiation and rendered the cells sensitive to NO-induced apoptosis. Therefore, SgII represents a key AP-1-regulated protein that counteracts NO toxicity and mediates neuronal differentiation of neuroblastoma cells.
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页码：879 / 888
页数：9
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