Two-steps control of cellular prion physiology by the Extracellular Regulated Kinase-1 (ERK1).

Description

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 PrPc 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.

Abstract

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