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Genetic evidence that small maf proteins are essential for the activation of antioxidant response element-dependent

Fumiki Katsuoka1, Hozumi Motohashi, Tetsuro Ishii

  • 1Center for TARA, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan.

Molecular and Cellular Biology
|September 2, 2005
PubMed

Insights

Small Maf proteins are crucial for activating antioxidant response element (ARE)-dependent genes. This study demonstrates their essential role in the inducible expression of many ARE genes, impacting cellular oxidative stress response.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cellular Biology

Background:

  • Small Maf proteins are implicated in Nrf2-mediated gene activation.
  • The precise requirement of small Mafs for antioxidant response element (ARE)-dependent genes needs further clarification.

Purpose of the Study:

  • To investigate the essentiality of small Maf proteins in the inducible expression of ARE-dependent genes.
  • To elucidate the specific roles of MafG, MafF, and MafK in the Nrf2-ARE pathway.

Main Methods:

  • Generation of mafG::mafF double-mutant mice and mafG::mafK::mafF triple-mutant fibroblasts.
  • Analysis of NAD(P)H:quinone oxidoreductase 1 (NQO1) and other ARE-dependent genes' induction.
  • Assessment of cellular susceptibility to oxidative stress.

Main Results:

  • Induction of NQO1 was impaired in double-mutant mice and keap1-null backgrounds lacking MafG and MafF.
  • MafK also contributes to ARE-dependent gene induction.
  • Triple-mutant cells lacking all small Mafs showed abolished induction of a wider range of ARE genes and increased oxidative stress susceptibility.

Conclusions:

  • Small Maf proteins are critical for the inducible expression of a significant subset of ARE-dependent genes.
  • The absence of small Mafs leads to heightened susceptibility to oxidative stress.
  • These findings highlight the indispensable role of small Mafs in the cellular antioxidant defense system.

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