Given our laboratory’s experience in studying polyomavirus mediated transformation, we initiated studies of Merkel cell polyomavirus (MCPyV) LT and ST. We determined that MCPyV ST specifically recruits MYCL to the EP400 complex and transactivates a large number of downstream target genes. Importantly, there are several druggable downstream targets of the ST-MYCL-EP400 complex including MDM2 and LSD1 (KDM1A). We have generated a mouse knock-in model capable of tissue specific expression of MCC tumor-derived MCPyV truncated LT and intact ST and demonstrated their oncogenic potential in vivo.

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