Upregulation of endogenous HMOX1 expression by a computer-designed artificial transcription factor.
Heme oxygenase-1 (HO-1) is well known as a cytoprotective factor. Research has revealed that it is a promising therapeutic target for cardiovascular diseases. In the current study, an HMOX1 (HO-1 gene) enhancer-specific artificial zinc-finger protein (AZP) was designed using bioinformatical methods. Then, an artificial transcription factor (ATF) was constructed based on the AZP. In the ATF, the p65 functional domain was used as the effector domain (ED), and a nuclear localization sequence (NLS) was also included. We next analyzed the affinity of the ATF to the HMOX1 enhancer and the effect of the ATF on endogenous HMOX1 expression. The results suggest that the ATF could effectively upregulate endogenous HMOX1 expression in ECV304 cells. With further research, the ATF could be developed as a potential drug for cardiovascular diseases.
Guo
Hongfeng
H
Department of Anatomy, Third Military Medical University, Sha-Ping-Ba District, Chongqing, China.
Tian
Yi
Y
Lu
Hai
H
Wei
Yong
Y
Ying
Dajun
D
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D019295:Computational Biology / Q000379:methods; D055808:Drug Discovery; D004742:Enhancer Elements, Genetic; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015202:Protein Engineering / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D016335:Zinc Fingers
D019913:Nuclear Localization Signals; D011993:Recombinant Fusion Proteins; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1