Molecular and Cellular Control of the Nrf1 Transcription Factor : An Integral Membrane Glycoprotein

ISBN-13: 9783639148411 / Angielski / Miękka / 2009 / 264 str.

Yiguo Zhang

Opis

This study has revealed that Nrf1 is an integralmembrane glycoprotein with transmembrane andextramembrane regions, located in both theendoplasmic reticulum (ER) and the nuclear envelope.This CNC/bZIP protein is targeted and anchored in theER through its N-terminal Homology Box 1 (NHB1)sequence, and in the ER lumen it is glycosylated byamide-linked attachment of glycans to the asparagineswithin its NST domain. After being correctly foldedinto a proper topology, mature Nrf1 protein could besorted out into the nuclear envelope. Once reachingthe inner nuclear membrane, it can gain access to thepromoter regions of its target genes and relevanttranscriptional mechineries in the nucleoplasm. Itshould be noted that, although Nrf1 is integrated inthe ER membrane, it is not activated by ER stressors,and conversely,they were foundto inhibit activation of this factor by a redoxinducer tBHQ. Therefore, Nrf1 may functionessentially as a control of redox compartmentizationfor maintaining redox homeostasis between the ER andnucleus; the former is a more oxidizing environmentin the cell, whereas the latter is a more reducing conpartment.