Induction of the PAC1-R (PACAP-type I receptor) gene by p53 and Zac

Pituitary adenylate cyclase-activating polypeptides and PAC1-R are expresse d during early embryogenesis and PACAP's neurotrophic action supports a rol e in neuronal development. In the adult brain PACAP functions as a neuropro tective factor that attenuates the neuronal damage resulting from various i nsults. The tumor suppressor gene p53 and the new zinc finger protein Zac r egulate apoptosis and cell cycle arrest through unrelated pathways and both genes are up-regulated under cerebral ischemia. We report here that p53 an d Zac induce expression of the PAC1-R gene. By this mechanism p53 and Zac c ould fine-tune the balance between death promoting and protective signals a nd may thus fulfil a dual role in ischemia. (C) 1999 Elsevier Science B.V. All rights reserved.