Glucocorticoid-dependent action of neural crest factor AP-2: Stimulation of phenylethanolamine N-methyltransferase gene expression

Ebert, S.N.; Ficklin, M.B.; Her, S.; Siddall, B.J.; Bell, R.A.; Ganguly, K.; Morita, K.; Wong, D.L.

Journal of Neurochemistry 70(6): 2286-2295


ISSN/ISBN: 0022-3042
PMID: 9603193
DOI: 10.1046/j.1471-4159.1998.70062286.x
Accession: 008737879

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AP-2 is a vertebrate transcription factor expressed in neural crest cells and their derivative tissues, including the adrenal medulla, where epinephrine is produced. AP-2 is shown to stimulate expression of the gene encoding the epinephrine biosynthetic enzyme phenylethanolamine N-methyltransferase (PNMT). However, stimulation of the PNMT gene by AP-2 requires glucocorticoids and appears to be mediated through the interaction of AP-2 with activated type II glucocorticoid receptors. Mutation of AP-2 and/or glucocorticoid receptor binding elements within the PNMT promoter disrupts the ability of AP-2 and glucocorticoids to induce PNMT promoter activity. These findings suggest, in the case of PNMT, that AP-2 stimulates gene expression through a novel glucocorticoid-dependent mechanism.