Glycogen synthase kinase 3 regulates expression of nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) and inhibits pro-survival function of Nrf1

Biswas, Madhurima; Kwong, Eric; Park, Eujean; Nagra, Parminder; Chan, Jefferson Y.

doi:10.1016/j.yexcr.2013.04.013

Cited by 31 publications

(26 citation statements)

References 42 publications

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“…5A, upper and lower panels ); this was, however, accompanied by decreased expression level of the ∼120kDa mNrf1 glycoprotein ( middle panel ). Taken together with other MG132‐based experimental evidence showing that the turnover of Nrf1/TCF11 occurs via Hrd1‐, SCF β‐TrCP ‐ and/or SCF FBW7 ‐directed ubiquitin‐mediated protein degradation pathways [22,57–59], it is therefore postulated that O ‐GlcNAcylation of mNrf1 by OGT enables destabilization of the CNC‐bZIP protein, possibly via the ubiquitin‐proteasomal degradation pathway, albeit detailed mechanistic studies are required.…”

Section: Resultsmentioning

confidence: 99%

Transcription factor Nrf1 is negatively regulated by its O‐GlcNAcylation status

et al. 2015

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a b s t r a c tO-Linked N-acetylglucosamine transferase (OGT) was identified as an Nrf1-interacting protein.Herein, we show that Nrf1 enables interaction with OGT and their co-immunoprecipitates are O-GlcNAcylated by the enzyme. The putative O-GlcNAcylation negatively regulates Nrf1/TCF11 to reduce both its protein stability and transactivation activity of target gene expression. The turnover of Nrf1 is enhanced upon overexpression of OGT, which promotes ubiquitination of the CNC-bZIP protein. Furthermore, the serine/theorine-rich sequence of PEST2 degron within Nrf1 is identified to be involved in the protein O-GlcNAcylation by OGT. Overall, Nrf1 is negatively regulated by its O-GlcNAcylation status that depends on the glucose concentrations.

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Section: Resultsmentioning

confidence: 99%

Transcription factor Nrf1 is negatively regulated by its O‐GlcNAcylation status

et al. 2015

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“…Several studies have shown that Nrf1 is regulated by phosphorylation. Glycogen Synthase Kinase 3 (GSK3) was previously demonstrated to negatively regulate Nrf1a stability [69]. Phosphorylation of Nrf1a facilitated by GSK3 was shown to recruit Fbw7, the Fbox containing ubiquitin ligase, for proteasomal degradation of Nrf1a.…”

Section: Discussionmentioning

confidence: 99%

Nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) is regulated by O-GlcNAc transferase

Han

Valdez

et al. 2017

Free Radical Biology and Medicine

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A B S T R A C TThe Nrf1 (Nuclear factor E2-related factor 1) transcription factor performs a critical role in regulating cellular homeostasis. Using a proteomic approach, we identified Host Cell Factor-1 (HCF1), a co-regulator of transcription, and O-GlcNAc transferase (OGT), the enzyme that mediates protein O-GlcNAcylation, as cellular partners of Nrf1a, an isoform of Nrf1. Nrf1a directly interacts with HCF1 through the HCF1 binding motif (HBM), while interaction with OGT is mediated through HCF1. Overexpression of HCF1 and OGT leads to increased Nrf1a protein stability. Addition of O-GlcNAc decreases ubiquitination and degradation of Nrf1a. Transcriptional activation by Nrf1a is increased by OGT overexpression and treatment with PUGNAc. Together, these data suggest that OGT can act as a regulator of Nrf1a.

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“…A previous study showed that the dys-regulation NFE2L1 protein might lead tumor [11]. Another study also suggested that NFE2L1 expression is related to the cell survival under stress condition [12]. A recent study found that USP15 protein regulates the TGF-β pathway and USP15 has an important International Journal of Bioscience, Biochemistry and Bioinformatics role in glioblastoma cancer [13].…”

Section: Resultsmentioning

confidence: 99%

Estimation of Drug Treatment Effects on the Signaling Pathways

Erce¹,

Işık²

2017

IJBBB

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Developing a computational method to observe cell behaviors can help to understand the expected outcome of a drug treatment even before doing the wet-lab experiments. The main goal of this research is computing the effects of a drug treatment in the signaling level for a better understanding of cellular responses after a drug treatment. The proposed algorithm can work on various biological networks to quantitatively evaluate the effects of a drug treatment in the cell by using gene expression data. The method was applied on the integrated KEGG signaling pathway and the most effected proteins were identified after the application of 14 different drugs on lymphoma cells. The results showed that the most affected proteins are not the direct target proteins of the given drugs. Indeed, the protein activities in the distant parts of signaling pathways are highly changed upon drug treatments. The literature validation showed that some of the proteins, which are commonly effected by the treatment of several drugs, have cancer related cellular activities as well.

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Glycogen synthase kinase 3 regulates expression of nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) and inhibits pro-survival function of Nrf1

Cited by 31 publications

References 42 publications

Transcription factor Nrf1 is negatively regulated by its O‐GlcNAcylation status

Transcription factor Nrf1 is negatively regulated by its O‐GlcNAcylation status

Nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) is regulated by O-GlcNAc transferase

Estimation of Drug Treatment Effects on the Signaling Pathways

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