AKT1 is positively regulated by G-quadruplexes in its promoter and 3'-UTR
| Autor: | Lanlan Zhang, Yunxuan Wang, Ting Yan, Guangchao Sui, Wenmeng Wang, Daniel B. Stovall, Qiong Wu, Guangyue Li, Yuhua Li, Dangdang Li |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Untranslated region Circular dichroism Biophysics G-quadruplex Biochemistry 03 medical and health sciences 0302 clinical medicine Neoplasms Gene expression Humans Binding site Promoter Regions Genetic Molecular Biology 3' Untranslated Regions Binding Sites Oligonucleotide Chemistry Three prime untranslated region Circular Dichroism Cell Biology Molecular biology Footprinting G-Quadruplexes Gene Expression Regulation Neoplastic 030104 developmental biology 030220 oncology & carcinogenesis embryonic structures Proto-Oncogene Proteins c-akt |
| Zdroj: | Biochemical and biophysical research communications. 561 |
| ISSN: | 1090-2104 |
| Popis: | AKT1 plays a key role in cell growth and survival, and its activation in cancers is mediated by different mechanisms. In this study, we investigated the potential of G-quadruplex (G4) formation by multiple consecutive G-tracts in the AKT1 promoter and its 3'-UTR. In circular dichroism analyses, synthetic oligonucleotides based on these G-tract regions showed molar ellipticity peaks at specific wavelengths of G4 structures. We verified G4 forming potential of these oligonucleotides using dimethyl sulfate footprinting, gel-shift and immunostaining assays. In reporter assays, mutations of the G-tracts in either the promoter or the 3'-UTR of AKT1 reduced expression mediated by these G-rich regions, suggesting positive regulation of AKT1 gene expression by these G4 structures. Furthermore, SP1 bound to its consensus sites regardless of the presence of G4 motifs in the AKT1 promoter, and both the G4 motifs and SP1 binding sites were needed to reach the strongest promoter strength. |
| Databáze: | OpenAIRE |
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