hBVR Regulation of STAT1
Human biliverdin reductase appears to play a regulatory role in IFN-γ mediated signal transduction in normal and cancerous cells. Examination of downstream targets in the signaling pathway has shown that of phosphorylation STAT-1, STAT-3 and Akt were increased within 10 minutes of IFN-γ treatment. IFN-γ also increases BVR mRNA expression within 12 hours of treatment in these cells. On the other hand, there was a significant increase in BVR mRNA expression after 3 hours of IFN-γ treatment in MCF-7 breast cancer cells. Overexpression of STAT-1, hBVR or a combination of STAT-1/BVR was ineffective in altering STAT-1 phosphorylation mediated by IFN-γ.
However, a peptide based on the hBVR primary sequence inhibited IFN-γ-mediated STAT-1 phosphorylation in BVR transfected cells. It is possible, therefore, that this BVR-specific peptide might be inducing cell proliferation in HEK cells. In hepatocellular carcinoma cells, BVR over-expression causes inhibition of IFN-γ-mediated β-catenin phosphorylation. These preliminary studies are suggestive of different roles for hBVR in STAT-1 signaling in normal and cancerous cells. Questions as to the functions of hBVR in STAT-1 signaling are currently being pursued. We plan to expand this line of investigation to other forms of STAT and JACK, which control different cell signaling pathways.
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