Nrf2, a Cap'n'Collar (CNC) basic leucine zipper (bZIP) transcription factor, regulates the induction of the heme oxygenase-1 (HO-1) gene. Stress response elements (StREs) in the HO-1 gene promoter are recognized by multiple transcription factors, including AP-1, Maf, and CNC-bZIP proteins. In L929 cells, CNC-bZIP proteins, particularly Nrf2, significantly activate the HO-1 enhancer. Nrf2 exhibits the highest transactivation activity, up to 30-fold, compared to other factors. A dominant-negative mutant of Nrf2 (Nrf2M) was generated and shown to inhibit HO-1 gene induction by 85-95% in response to various inducers, including heme, cadmium, zinc, arsenite, and tert-butylhydroquinone. In contrast, a dominant-negative mutant of c-Jun did not inhibit HO-1 gene activation, suggesting that Nrf2 is a key regulator of HO-1 gene expression. Nrf2 does not homodimerize but forms heterodimers with small Maf proteins or Jun proteins. However, co-expression of Jun proteins or p18 did not significantly affect Nrf2-mediated trans-activation. These findings suggest that Nrf2 functions as a heterodimer with a partner other than p18 or Jun proteins. Nrf2 and small Maf proteins form heterodimers that bind to NF-E2 binding sites and may regulate transcription. However, Nrf2-p18 heterodimers do not activate the HO-1 gene, as evidenced by their inability to bind the StRE of the HO-1 gene. This indicates that Nrf2 may not function as a heterodimer with p18 in HO-1 gene regulation. Nrf2 is a potent positive regulator of the HO-1 gene and mediates inducer-dependent gene activation. Nrf2 functions as an obligate heterodimer, but the partner(s) necessary for HO-1 gene regulation are not known. Nrf2 is not p18 or a member of the known Jun family of proteins. Studies to identify the Nrf2 partner are currently in progress. The results suggest that Nrf2 plays a crucial role in the induction of the HO-1 gene, which is involved in the cellular defense mechanism against oxidant stress.Nrf2, a Cap'n'Collar (CNC) basic leucine zipper (bZIP) transcription factor, regulates the induction of the heme oxygenase-1 (HO-1) gene. Stress response elements (StREs) in the HO-1 gene promoter are recognized by multiple transcription factors, including AP-1, Maf, and CNC-bZIP proteins. In L929 cells, CNC-bZIP proteins, particularly Nrf2, significantly activate the HO-1 enhancer. Nrf2 exhibits the highest transactivation activity, up to 30-fold, compared to other factors. A dominant-negative mutant of Nrf2 (Nrf2M) was generated and shown to inhibit HO-1 gene induction by 85-95% in response to various inducers, including heme, cadmium, zinc, arsenite, and tert-butylhydroquinone. In contrast, a dominant-negative mutant of c-Jun did not inhibit HO-1 gene activation, suggesting that Nrf2 is a key regulator of HO-1 gene expression. Nrf2 does not homodimerize but forms heterodimers with small Maf proteins or Jun proteins. However, co-expression of Jun proteins or p18 did not significantly affect Nrf2-mediated trans-activation. These findings suggest that Nrf2 functions as a heterodimer with a partner other than p18 or Jun proteins. Nrf2 and small Maf proteins form heterodimers that bind to NF-E2 binding sites and may regulate transcription. However, Nrf2-p18 heterodimers do not activate the HO-1 gene, as evidenced by their inability to bind the StRE of the HO-1 gene. This indicates that Nrf2 may not function as a heterodimer with p18 in HO-1 gene regulation. Nrf2 is a potent positive regulator of the HO-1 gene and mediates inducer-dependent gene activation. Nrf2 functions as an obligate heterodimer, but the partner(s) necessary for HO-1 gene regulation are not known. Nrf2 is not p18 or a member of the known Jun family of proteins. Studies to identify the Nrf2 partner are currently in progress. The results suggest that Nrf2 plays a crucial role in the induction of the HO-1 gene, which is involved in the cellular defense mechanism against oxidant stress.