The Nrf1 CNC/bZIP protein is a nuclear envelope-bound transcription factor that is activated by t-butyl hydroquinone but not by endoplasmic reticulum stressors

Yiguo Zhang, John M. Lucocq, John D. Hayes

    Research output: Contribution to journalArticle

    50 Citations (Scopus)

    Abstract

    In rat liver RL-34 cells, endogenous Nrf1 (nuclear factor-erythroid 2 p45 subunit-related factor 1) is localized in the ER (endoplasmic reticulum) where it exists as a glycosylated protein. Electron microscopy has demonstrated that. ectopic Nrf1 in COS-I cells is located in the ER and the NE (nuclear envelope). Subcellular fractionation, together with I membrane proteinase protection assay, revealed that Nrf1 is an integral membrane protein with both luminal anti cytoplasmic domains. The N-terminal 65 residues of Nrf1 direct its integration into the ER and NE membranes and tether it to a Triton X-100-resistant membrane microdomain that is associated with lipid rafts. The activity of Nrf1 was increased by the electrophile tBHQ (t-butyl hydroquinone) probably through an N-terminal domain-dependent process. We found that the NST (Asn/Ser/Thr-rich) domain, along with AD1 (acidic domain 1), contributes positively to the transactivation activity of full-length Nrf1. Furthermore, the NST domain contains seven putative-Asn-Xaa-Ser/Thr- glycosylation sites and, when glycosylation

    Original languageEnglish
    Pages (from-to)293-310
    Number of pages18
    JournalBiochemical Journal
    Volume418
    DOIs
    Publication statusPublished - 1 Mar 2009

    Keywords

    • detergent-resistant membrane
    • endoplasmic reticulum stress
    • glycosylation
    • nuclear factor-erythroid 2 p45 subunit-related factor 1 (Nrf1)
    • nuclear envelope
    • oxidative stress
    • transcriptional regulation
    • ANTIOXIDANT RESPONSE ELEMENT
    • LEUCINE-ZIPPER
    • TERT-BUTYLHYDROQUINONE
    • TRANSMEMBRANE DOMAIN
    • INDUCIBLE EXPRESSION
    • EMBRYONIC LETHALITY
    • MEMBRANE-PROTEINS
    • OXIDATIVE STRESS
    • CELL-SURVIVAL
    • FACTOR TCF11

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