An APE1 inhibitor reveals critical roles of the redox function of APE1 in KSHV replication and pathogenic phenotypes

• DOI: 10.1371/journal.ppat.1006289
• Publication Date: 2017-04-05T18:53:17Z
• Authors: Canrong Zhong; Mengyang Xu; Yan Wang; Jun Xu; Yan Yuan
• Keywords: Lytic cycle; Transcription

APE1 is a multifunctional protein with DNA base excision repair function in its C-terminal domain and redox activity N-terminal domain. The of converts certain transcription factors from inactive oxidized to active reduced forms. Given that among the APE1-regulated many are critical for KSHV replication pathogenesis, we investigated whether inhibition blocks Kaposi's sarcoma (KS) phenotypes. With an shRNA-mediated silencing approach known APE-1 inhibitor, demonstrated indeed required as well KSHV-induced angiogenesis, validating therapeutic target KSHV-associated diseases. A ligand-based virtual screening yielded small molecular compound, C10, which proven bind APE1. C10 exhibits low cytotoxicity but efficiently inhibits lytic (EC50 0.16 μM selective index 165) KSHV-mediated pathogenic phenotypes including cytokine production, angiogenesis cell invasion, demonstrating potential become effective drug treatment KS.