共查询到20条相似文献,搜索用时 31 毫秒
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Evolutionary conserved N-terminal domain of Nrf2 is essential for the Keap1-mediated degradation of the protein by proteasome 总被引:1,自引:0,他引:1
Katoh Y Iida K Kang MI Kobayashi A Mizukami M Tong KI McMahon M Hayes JD Itoh K Yamamoto M 《Archives of biochemistry and biophysics》2005,433(2):342-350
Under homeostatic conditions, Nrf2 activity is constitutively repressed. This process is dependent on Keap1, to which Nrf2 binds through the Neh2 domain. Since the N-terminal subdomain of Neh2 (Neh2-NT) contains evolutionarily conserved motifs, we examined the roles they play in the degradation of Nrf2. In Neh2-NT, we defined a novel motif that is distinct from the previously characterized DIDLID motif and designated it DLG motif. Deletion of Neh2-NT or mutation of the DLG motif largely abolished the Keap1-mediated degradation of Nrf2. These mutations were found to enfeeble the binding affinity of Nrf2 to Keap1. The Neh2-NT subdomain directed DLG-dependent, Keap1-independent, degradation of a reporter protein in the nucleus. By contrast, mutation of DLG did not affect the half-life of native Nrf2 protein in the nucleus under oxidative stress conditions. These results thus demonstrate that DLG motif plays essential roles in the Keap1-mediated proteasomal degradation of Nrf2 in the cytoplasm. 相似文献
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Osada M Inaba R Shinohara H Hagiwara M Nakamura M Ikawa Y 《Biochemical and biophysical research communications》2001,283(5):1135-1141
The amino terminal of human P51/TAp63, a P53 homologue, possesses a transactivation domain involved in the activation of its target genes by binding to DNA elements responsive to the p53 protein family. Using a series of amino terminal deletions, the transactivation domain was mapped between amino acid residues 50 to 69. This domain also regulates protein stability in a proteasome-dependent manner, and Ser51 and Ser68 were found to be essential for this stability. Our results suggest that P51 activity is greatly affected by protein stability. 相似文献
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C Venot M Maratrat C Dureuil E Conseiller L Bracco L Debussche 《The EMBO journal》1998,17(16):4668-4679
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