Differential effects of HTLV-1 Tax oncoprotein on the different estrogen-induced-ER alpha-mediated transcriptional activities

作者：Abou Kandil Ammar; Eisa Nora; Jabareen Azhar; Huleihel Mahmoud^*

来源：Cell Cycle, 2016, 15(19): 2626-2635.

DOI：10.1080/15384101.2016.1208871

• BRCA-1
• ER alpha
• ERE
• HTLV-1
• Tax

The activated estrogen (E2) receptor alpha (ER alpha) is a potent transcription factor that is involved in the activation of various genes by 2 different pathways; a classical and non-classical. In classical pathway, ER alpha binds directly to E2-responsive elements (EREs) located in the appropriate genes promoters and stimulates their transcription. However, in non-classical pathway, the ER alpha can indirectly bind with promoters and enhance their activity. For instance, ER alpha activates BRCA1 expression by interacting with jun/fos complex bound to the AP-1 site in BRCA1 promoter. Interference with the expression and/or functions of BRCA1, leads to high risk of breast or/and ovarian cancer. HTLV-1Tax was found to strongly inhibit BRCA1 expression by preventing the binding of E2-ER alpha complex to BRCA1 promoter. Here we examined Tax effect on ER alpha induced activation of genes by the classical pathway by testing its influence on E2-induced expression of ERE promoter-driven luciferase reporter (ERE-Luc). Our findings showed that E2 profoundly stimulated this reporter expression and that HTLV-1Tax significantly induced this stimulation. This result is highly interesting because in our previous study Tax was found to strongly block the E2-ER alpha-mediated activation of BRCA1 expression. ER alpha was found to produce a big complex by recruiting various cofactors in the nucleus before binding to the ERE region. We also found that only part of the reqruited cofactors are required for the transcriptional activity of ER alpha complex. Chip assay revealed that the binding of Tax to the ER alpha complex, did not interfere with its link to ERE region.

• 出版日期2016