KSHV vPK inhibits Wnt signaling via preventing interactions between beta-catenin and TCF4

Abstract

Viral factors interact with host cellular proteins, leading to dysregulation of signaling pathways. The Wnt pathway is known to participate in embryonic development and oncogenesis under dysregulation conditions. A downstream factor of the Wnt signaling pathway, beta-catenin, activates T-cell factor (TCF)-dependent transcription, which contributes to cell proliferation and tumorigenesis. In this study, we demonstrated that viral protein kinase (vPK) encoded by Kaposi's sarcoma-associated herpesvirus inhibits the Wnt signaling pathway without affecting nuclear localization and expression of beta-catenin. Coimmunoprecipitation and chromatin immunoprecipitation assays revealed that vPK interacts with beta-catenin, reducing the binding affinity on TCF binding regions as well as interactions of beta-catenin with TCF4. Overexpression of vPK led to reduced mRNA expression of cyclin D1, a well-known transcriptional product of Wnt signaling, suggesting that vPK effectively regulates the host signaling pathway through direct interactions with cellular proteins. (C) 2018 Elsevier Inc. All rights reserved.