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

Jiayu Chen; Xiping Liu; Fenglin Lü; Xinping Liu; Yi Ru; Yonggang Ren; Libo Yao; Yiguo Zhang

doi:10.1016/j.febslet.2015.07.030

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

FEBS Lett. 2015 Aug 19;589(18):2347-58. doi: 10.1016/j.febslet.2015.07.030. Epub 2015 Jul 29.

Authors

Jiayu Chen¹, Xiping Liu², Fenglin Lü³, Xinping Liu⁴, Yi Ru⁴, Yonggang Ren³, Libo Yao⁴, Yiguo Zhang⁵

Affiliations

¹ Laboratory of Cell Biochemistry and Gene Regulation, College of Medical Bioengineering and Faculty of Life Sciences, University of Chongqing, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China; Department of Biochemistry and Molecular Biology, Zunyi Medical College, Zunyi 563000, China; State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China.
² Department of Biochemistry and Molecular Biology, Zunyi Medical College, Zunyi 563000, China; State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China.
³ Laboratory of Cell Biochemistry and Gene Regulation, College of Medical Bioengineering and Faculty of Life Sciences, University of Chongqing, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China.
⁴ State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an 710032, China.
⁵ Laboratory of Cell Biochemistry and Gene Regulation, College of Medical Bioengineering and Faculty of Life Sciences, University of Chongqing, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China. Electronic address: yiguozhang@cqu.edu.cn.

PMID: 26231763
DOI: 10.1016/j.febslet.2015.07.030

Abstract

O-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.

Keywords: Nuclear factor erythroid 2-related factor (Nrf1); O-GlcNAcylation; O-Linked N-acetylglucosamine transferase (OGT); Post-translational modification; Transcriptional regulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylglucosamine / metabolism*
Amino Acid Sequence
Animals
Antioxidants / metabolism
Gene Knockdown Techniques
Glycosylation
HEK293 Cells
Humans
Mice
Molecular Sequence Data
N-Acetylglucosaminyltransferases / deficiency
N-Acetylglucosaminyltransferases / genetics
N-Acetylglucosaminyltransferases / metabolism
NF-E2-Related Factor 1 / chemistry
NF-E2-Related Factor 1 / metabolism*
Protein Stability
Repressor Proteins / metabolism
Response Elements / genetics
Transcriptional Activation

Substances

Antioxidants
NF-E2-Related Factor 1
NFE2L1 protein, human
Repressor Proteins
N-Acetylglucosaminyltransferases
N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase
Acetylglucosamine