Authors
L. Li, A. C. Hung & A.G. Porter, IMCB, Singapore.

Correspondence to Alan G. Porter, mcbagp@imcb.a-star.edu.sg

Abstract
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) up-regulated sgII mRNA dependent on a CRE element in the sgII promoter, and NO stimulated SgII protein secretion in neuroblastoma cells. Up-regulation 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 (NGF)-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.



Published in Cell Death & Differentiation. 2008, February 1; doi:10.1038/cdd.2008.8.

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