Loss Of Epithelial Selenoprotein-P Impairs Epithelial Oxidant Defenses And Enhances Colitis-Associated Carcinogenesis

of GFP and/or hMSH3-FLAG.Results: In the context of individual signals , cells transfected with NLS1-GFP and NLS2-GFP, but not NLS3-GFP, showed exclusive and predominant nuclear signal respectively.NES1-NES2-GFP, but not NES1-and/or NES2-GFP, led to cytoplasmic GFP upon IL-6 treatment.Mutation experiments abolished the observed wild type localizations.In the context of full length hMSH3-FLAG, deletion of NLS1, but not NLS2, resulted in cytosolic presence of hMSH3-FLAG.Deletion of both NESs abolished the hMSH3-FLAG cytosolic shift in response to IL-6 treatment.Conclusion: We have identified the specific NLS permitting hMSH3's nuclear import and the specific NESs directing its export in response to IL-6.Experiments using deletion constructs of hMSH3 showed that NLS1 directs hMSH3's nuclear import, and NES1 and NES2 work together to effectively export hMSH3 in response to IL-6.hMSH3's shuttling behavior likely enables inflammation to trap hMSH3 in the cytoplasm, allowing mutations to occur and furthering mal-behavior of cancer cells.