Two-steps control of cellular prion physiology by the extracellular regulated kinase-1 (ERK1)

Abstract

Cellular prion (PrP C) undergoes a regulated α-secretase- like cleavage by the disintegrin ADAM17 similar to the one taking place on β-Amyloid Precursor Protein (βAPP). Because these cleavages give rise to biologically active fragments, understanding their regulation could be of importance. We have established that the Extracellular Regulated Kinase-1 (ERK1) controls PrP C processing by modulating ADAM17 phosphorylation in a protein kinase C-dependent manner. Strikingly, we also demonstrated that ERK1 acts upstream to increase PrP C promoter transactivation in an AP-1 dependent manner. Therefore, ERK1 exerts a dual control of both PrP C metabolism and expression. Interestingly, α-secretase cleavage of βAPP appears to be independent of ERK1. I describe here similarities and differences in α-secretase-mediated PrP C and βAPP processing pathways and discuss putative physiopathological implications. © 2012 Landes Bioscience.