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.

@article{Zhang2009TheNC,
  title={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.},
  author={Yiguo Zhang and John Milton Lucocq and John D. Hayes},
  journal={The Biochemical journal},
  year={2009},
  volume={418 2},
  pages={
          293-310
        }
}
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-1 cells is located in the ER and the NE (nuclear envelope). Subcellular fractionation, together with a membrane proteinase protection assay, revealed that Nrf1 is an integral membrane protein with both luminal and cytoplasmic domains. The N… 
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The Nrf1 CNC-bZIP Protein Is Regulated by the Proteasome and Activated by Hypoxia

The data suggests that Nrf1 is controlled by several post-translational mechanisms, including ubiquitination, proteolytic processing and proteasomal-mediated degradation as well as by its phosphorylation status.

Activation of the membrane-bound Nrf1 transcription factor by USP19, a ubiquitin-specific protease C-terminally anchored in the endoplasmic reticulum.

Transcription Factor Nrf1 Is Topologically Repartitioned across Membranes to Enable Target Gene Transactivation through Its Acidic Glucose-Responsive Domains

A hitherto unknown mechanism by which the transactivation activity of Nrf1 is controlled through its membrane-topology is reported, which dictates its post-translational modifications which together control its ability to transactivate target genes.

Activation of the membrane-bound Nrf1 transcription factor by USP19, a ubiquitin-specific protease C-terminally tail-anchored in the endoplasmic reticulum

It is found that Nrf1 stability and transactivity are enhanced by USP19, a tail-anchored ubiquitin-specific protease in the endoplasmic reticulum (ER), and it is unraveled that transcriptional expression of endogenous USP 19 and its promoter-driven reporter genes is regulated by Nrf2, as well by NRF1, at distinct layers within a complex hierarchical regulatory network.

Identification of topological determinants in the N-terminal domain of transcription factor Nrf1 that control its orientation in the endoplasmic reticulum membrane.

Experimental data is presented showing that the signal peptide of Nrf1 contains a TM1 (transmembrane 1) region that is orientated across the ER membrane in an N(cyt)/C(lum) fashion with its N-terminus facing the cytoplasm and its C- terminus positioned in the lumen of the ER.

The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity

Creative use of Gal4-based reporter assays with protease protection assays (GRAPPA and dFPP) reveals that the membrane-topogenic vectorial behaviour of Nrf1 dictates its post-translational modification and transactivation activity.

Unification of Opposites between Two Antioxidant Transcription Factors Nrf1 and Nrf2 in Mediating Distinct Cellular Responses to the Endoplasmic Reticulum Stressor Tunicamycin

A unity of opposites is reported between these two antioxidant transcription factors, Nrf1 and Nrf2, in coordinating distinct cellular responses to the ER stressor tunicamycin (TU).

The selective post-translational processing of transcription factor Nrf1 yields distinct isoforms that dictate its ability to differentially regulate gene expression

It is reported that AD1 and AD2 are required for the stability of the 120-kDa Nrf1 glycoprotein, but not that of the non-glycosylated/de-glyCosylated 95-k Da isoform.

Dual Regulation of the Transcriptional Activity of Nrf1 by β-TrCP- and Hrd1-Dependent Degradation Mechanisms

Results clearly suggest that both β-TrCP- and Hrd1-dependent degradation mechanisms regulate the transcriptional activity of Nrf1 to maintain cellular homeostasis.

A unity of opposites in between Nrf1- and Nrf2-mediated responses to the endoplasmic reticulum stressor tunicamycin

A unity of opposites is reported in both Nrf1- and Nrf2-coordinated responses to the ER stressor tunicamycin (TU) to maintain cell homeostasis by a series of coordinated ER-to-nuclear signaling responses to TU.
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