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Identification of essential regulatory elements responsible for the explicit expression of IL-28Rα and their effect
Hashaam Akhtar1, Gibrail Islam2, Syed Umer Jan3
1Atta-Ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.
Abstract:
IL-28Rα and IL10Rβ collectively construct a fully functional hetero-dimeric receptor for type III interferons (IFNs). IL-28Rα is the private chain for type III IFNs since their involvement in any other pathway has not been reported yet and they are highly expressed in response to certain viral attack or cancers. IL-28Rα is specific in their expression pattern and it expresses within few cell types only. The regulatory mechanisms governing the expression of IL-28Rα at the molecular level are not completely known yet and need to be scrutinized at primary levels. In the present study, various in-silico techniques were applied and it was observed that AP1-2, STAT 1-6, P-53, LyF-1 (lymphoid transcription factor), c-Jun, PU.1, CREB (cAMP response element-binding), PLAG (pleotropic adenoma gene), MYOD (myoblast determination protein 1), NOFL and KLFS as transcription factors that are selected with preference. Interestingly AP-2, c-Jun, LyF-1, STAT, NF-Y and P53 have also been reported in literature recently as some of the key regulatory elements as well. Based on the fact that interlinking between different interferon stimulation genes (ISGs) is also not very clear and induction of one type of interferon can affect the efficacy of the other, we found that IFN-λ4 induction can increase the expression of IL-28Rα, similar to IFN-λ3 but contrary to type I IFNs, which has either no effect on the expression of IL-28Rα or can down regulate its expression at higher concentrations (data not published).
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