The study investigates the role of Nrf2, a Cap'n'Collar transcription factor, in the induction of the heme oxygenase-1 (HO-1) gene. Nrf2 is found to be a potent activator of the HO-1 gene, with a 25- to 30-fold increase in trans-activation compared to other CNC-bZIP proteins. A dominant-negative mutant of Nrf2, Nrf2M, was generated and conditionally expressed in L929 cells. Overexpression of Nrf2M inhibited HO-1 mRNA accumulation in response to various inducers, including heme, cadmium, zinc, arsenite, and tert-butylhydroquinone, by 85-95%. In contrast, overexpression of a dominant-negative mutant of c-Jun did not inhibit HO-1 gene activation but decreased cell growth. The study also examines the potential partners of Nrf2 in HO-1 gene regulation, finding that Nrf2 heterodimerizes with small Maf proteins but not with Jun proteins. The results suggest that Nrf2 is a key regulator of HO-1 gene induction, but its specific partner(s) remain to be identified.The study investigates the role of Nrf2, a Cap'n'Collar transcription factor, in the induction of the heme oxygenase-1 (HO-1) gene. Nrf2 is found to be a potent activator of the HO-1 gene, with a 25- to 30-fold increase in trans-activation compared to other CNC-bZIP proteins. A dominant-negative mutant of Nrf2, Nrf2M, was generated and conditionally expressed in L929 cells. Overexpression of Nrf2M inhibited HO-1 mRNA accumulation in response to various inducers, including heme, cadmium, zinc, arsenite, and tert-butylhydroquinone, by 85-95%. In contrast, overexpression of a dominant-negative mutant of c-Jun did not inhibit HO-1 gene activation but decreased cell growth. The study also examines the potential partners of Nrf2 in HO-1 gene regulation, finding that Nrf2 heterodimerizes with small Maf proteins but not with Jun proteins. The results suggest that Nrf2 is a key regulator of HO-1 gene induction, but its specific partner(s) remain to be identified.