Heterodimerization with small Maf proteins enhances nuclear retention of Nrf2 via masking the NESzip motif

Wenge Li, Siwang Yu, Tong Liu, Jung Hwan Kim, Volker Blank, Hong Li, A. N Tony Kong

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Nrf2 is the key transcription factor regulating the antioxidant response. When exposed to oxidative stress, Nrf2 translocates to cell nucleus and forms heterodimer with small Maf proteins (sMaf). Nrf2/sMaf heterodimer binds specifically to a cis-acting enhancer called antioxidant response element and initiates transcription of a battery of antioxidant and detoxification genes. Nrf2 possesses a NESzip motif (nuclear export signal co-localized with the leucine zipper (ZIP) domain). Heterodimerization with MafG via ZIP-ZIP binding enhanced Nrf2 nuclear retention, which could be abrogated by the deletion of the ZIP domain or site-directed mutations targeting at the ZIP domain. In addition, dimerization with MafG precluded Nrf2zip/CRM1 binding, suggesting that Nrf2/MafG heterodimerization may simultaneously mask the NESzip motif. MafG-mediated nuclear retention may enable Nrf2 proteins to evade cytosolic proteasomal degradation and consequently stabilize Nrf2 signaling. For the first time, we show that under the physiological condition, the NESzip motif can be switched-off by heterodimerization.

Original languageEnglish (US)
Pages (from-to)1847-1856
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1783
Issue number10
DOIs
StatePublished - Oct 2008
Externally publishedYes

Fingerprint

Maf Transcription Factors
Antioxidants
Antioxidant Response Elements
Nuclear Export Signals
Leucine Zippers
Dimerization
Masks
Cell Nucleus
Oxidative Stress
Transcription Factors
Mutation
Genes
Proteins

Keywords

  • CRM1
  • FRET
  • MafG
  • Nrf2
  • ZIP

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Biophysics

Cite this

Heterodimerization with small Maf proteins enhances nuclear retention of Nrf2 via masking the NESzip motif. / Li, Wenge; Yu, Siwang; Liu, Tong; Kim, Jung Hwan; Blank, Volker; Li, Hong; Kong, A. N Tony.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1783, No. 10, 10.2008, p. 1847-1856.

Research output: Contribution to journalArticle

Li, Wenge ; Yu, Siwang ; Liu, Tong ; Kim, Jung Hwan ; Blank, Volker ; Li, Hong ; Kong, A. N Tony. / Heterodimerization with small Maf proteins enhances nuclear retention of Nrf2 via masking the NESzip motif. In: Biochimica et Biophysica Acta - Molecular Cell Research. 2008 ; Vol. 1783, No. 10. pp. 1847-1856.
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