Hozumi Motohashi

The small Maf proteins, MafF, MafG, and MafK, possess a leucine zipper (Zip) domain that is required for homodimer or heterodimer complex formation with other bZip transcription factors. In this study we sought to determine the identity of the specific constituent that collaboratively interacts with Nrf2 to bind to the Maf recognition element in vivo. Studies in vitro suggested that Nrf2 forms heterodimers with small Maf proteins and then bind to Maf recognition elements, but the bona fide partn

Maf family proteins are so named because of their structural similarity to the founding member, the oncoprotein v-Maf. The small Maf proteins (MafF, MafG and MafK), as do all family members, include a characteristic basic region linked to a leucine zipper (b-Zip) domain which mediate DNA binding and subunit dimerization respectively. The small Maf proteins form homodimers or heterodimers with other b-Zip proteins present in the cell and bind to Maf recognition elements (MARE) in DNA. Since they

The Kelch-like ECH-associated protein 1/nuclear factor erythroid-derived 2-like 2 (KEAP1-NRF2) system is a pivotal defense mechanism against oxidative and electrophilic stress. Although transient NRF2 activation in response to stress is beneficial for health, persistent NRF2 activation in cancer cells has deleterious effects on cancer-bearing hosts by conferring therapeutic resistance and aggressive tumorigenic activity on cancer cells. Because NRF2 increases the antioxidant and detoxification c

p62/SQSTM1 is a selective substrate of autophagy, and aberrant accumulation of p62 has been observed in various pathological conditions. To understand the roles p62 plays in non-small-cell lung cancer (NSCLC), we carried out immunohistochemical analyses of p62 expression in a cohort of patients with annotated clinicopathological data. As analyses of murine and human hepatocellular carcinomas suggested a correlation between p62 and Nrf2 accumulations, we also examined NRF2 expression in the same

The mammalian brain is highly vulnerable to oxygen deprivation, yet the mechanism underlying the brain's sensitivity to hypoxia is incompletely understood. Hypoxia induces accumulation of hydrogen sulfide, a gas that inhibits mitochondrial respiration. Here, we show that, in mice, rats, and naturally hypoxia-tolerant ground squirrels, the sensitivity of the brain to hypoxia is inversely related to the levels of sulfide:quinone oxidoreductase (SQOR) and the capacity to catabolize sulfide. Silenci

Nrf2 accumulates in nuclei upon exposure to oxidative stress, heterodimerizes with a small Maf protein, and activates the transcription of stress target genes through antioxidant response elements (AREs). We found that diethyl maleate (DEM), a well known activator of Nrf2, induces one of the small Maf genes, mafG. To elucidate roles MafG might play in the oxidative stress response, we examined transcriptional regulation of the mouse mafG gene. MafG utilizes three independent first exons that are

In megakaryocytes, the maturation process and oxidative stress response appear to be closely related. It has been suggested that increased oxygen tension and reactive oxygen species (ROS) promote megakaryopoiesis and that the expression of stress-responsive genes responsible for ROS elimination declines during megakaryocytic maturation. NF-E2 p45 is an essential regulator of megakaryopoiesis, whereas Nrf2 is a key activator of stress-responsive genes. Because p45 and Nrf2 have similar DNA-bindin