Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9118745 | Neuropeptides | 2005 | 9 Pages |
Abstract
The rat preprotachykinin A (rtPPTA) promoter fragment spanning â865Â +Â 92, relative to the major transcriptional start, has previously been demonstrated to be nerve growth factor (NGF) responsive in primary cultures of rat dorsal root ganglion (DRG) neurones [Harrison, P.T., Dalziel, R.G., Ditchfield, N.A., Quinn, J.P., 1999. Neuronal-specific and nerve growth factor-inducible expression directed by the preprotachykinin-A promoter delivered by an adeno-associated virus vector. Neuroscience 94, 997-1003]. In this communication, we demonstrate that an E box element at â60, in part, regulates the activity of this rtPPT-A promoter fragment in DRG neurones in response to NGF. Differential regulation of the promoter is observed in the presence or absence of NGF when the E Box site is present. Under basal conditions binding of proteins to this â60 element may antagonise promoter activity. Hence, in the absence of NGF, mutation of the â60 E box increased reporter gene expression. Further, comparison of levels of reporter gene expression supported by both WT and mutated promoter indicate that in the presence of NGF the â60 E box element also plays a role as an activator domain. This represents a novel mechanism for NGF regulation of rtPPT-A. Similarly, an important role for this signalling pathway was observed in neonate rat DRG neuronal cultures, which require NGF for their survival, namely mutation of the â60 element resulted in higher levels of reporter gene expression.
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Authors
Lesley Gerrard, Mark Howard, Trevor Paterson, Thimmasettappa Thippeswamy, John P. Quinn, Kate Haddley,