Regulation of PrPC expression: nerve growth factor (NGF) activates the prion gene promoter through the MEK1 pathway in PC12 cells

Neuroscience Letters
Izabela ZawlikPiotr Rieske

Abstract

A high expression of PrP(C) in cells is one factor that increases the risk of conversion to the misfolded, disease-associated form (PrP(Sc)) characteristic of transmissible spongiform encephalopathies. Thus, developing a method to control the level of PrP(C) expression in cells could be one way to delay or prevent the onset of clinical signs of these diseases. In this study the mechanisms controlling the expression of the Prnp gene in PC12 cells and in rat brain were examined. We observed a slight activation of a cloned fragment of the human PRNP gene promoter using the luciferase reporter system in PC12 cells stimulated with nerve growth factor (NGF). The activating effect of NGF was enhanced by mitogen-activated protein kinase (MEK1) and suppressed by myristylated serine/threonine kinase (myrAKT). These results suggest that MEK1 is a positive activator of the PRNP promoter that inhibits the AKT pathway. Independent experiments suggested that high expression of PrP(C) in the brain depends on the rate of translation and/or the efficiency of PrP(C) stabilization. We also investigated the epigenic status of the Prnp promoter. We observed no increase of PrP(C) or Prnp mRNA levels in PC12 cells after treatment with the DNA-demethyl...Continue Reading

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Citations

Jan 19, 2013·Biochimie·Giuseppe Scalabrino, Daniela Veber
Sep 11, 2009·BMC Research Notes·Michael J TahenyWolfgang W Quitschke
Oct 20, 2015·Journal of the Neurological Sciences·Daniela Veber, Giuseppe Scalabrino
Apr 5, 2008·Molecular and Cellular Neurosciences·Yasmine AguibHermann M Schätzl
Nov 26, 2011·Experimental Neurology·Giuseppe ScalabrinoGiovanni Tredici
Nov 14, 2014·Cellular and Molecular Life Sciences : CMLS·C L HaighS J Collins
Apr 9, 2008·Physiological Reviews·Rafael LindenRicardo R Brentani
Nov 28, 2012·Clinical Chemistry and Laboratory Medicine : CCLM·Giuseppe Scalabrino, Daniela Veber
Apr 22, 2017·Frontiers in Molecular Biosciences·Andrew R Castle, Andrew C Gill

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