The cyclic AMP response element in the calcitonin/calcitonin gene-related peptide gene promoter is necessary but not sufficient for its activation by nerve growth factor.
The gene encoding calcitonin gene-related peptide (CGRP) is inducible by nerve growth factor (NGF) in primary dorsal root ganglion neurons. By transfecting these primary neurons, we have defined a region of the CGRP promoter from -140 to -72 relative to the transcriptional start site which is essential for its inducibility by NGF as well as by cyclic AMP and which can confer these responses on a heterologous promoter. A cyclic AMP response element (CRE) within this region is essential for both these responses which are abolished by site-directed mutagenesis of this element. In contrast to the intact fragment the isolated CRE can confer responsiveness to cyclic AMP but not NGF on a heterologous promoter. The reasons for the different role of the CRE in the response of the CGRP promoter to cyclic AMP and NGF are discussed.
Watson
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A
Department of Molecular Pathology, University College London Medical School, United Kingdom.
Latchman
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D
D000818:Animals; D001483:Base Sequence; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar
D009414:Nerve Growth Factors; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide