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Open AccessCommunication

Merkel Cell Polyomavirus Large T Antigen is Dispensable in G2 and M-Phase to Promote Proliferation of Merkel Cell Carcinoma Cells

1
Department of Dermatology, Venereology und Allergology, University Hospital Würzburg, 97080 Würzburg, Germany
2
Department of Pathology, Centre Hospitalier Universitaire De Tours, INRA UMR 1282 BIP, 37200 Tours, France
*
Author to whom correspondence should be addressed.
Viruses 2020, 12(10), 1162; https://doi.org/10.3390/v12101162
Received: 14 August 2020 / Revised: 12 October 2020 / Accepted: 13 October 2020 / Published: 14 October 2020
(This article belongs to the Special Issue Polyomaviruses)
Merkel cell carcinoma (MCC) is an aggressive skin cancer frequently caused by the Merkel cell polyomavirus (MCPyV), and proliferation of MCPyV-positive MCC tumor cells depends on the expression of a virus-encoded truncated Large T antigen (LT) oncoprotein. Here, we asked in which phases of the cell cycle LT activity is required for MCC cell proliferation. Hence, we generated fusion-proteins of MCPyV-LT and parts of geminin (GMMN) or chromatin licensing and DNA replication factor1 (CDT1). This allowed us to ectopically express an LT, which is degraded either in the G1 or G2 phase of the cell cycle, respectively, in MCC cells with inducible T antigen knockdown. We demonstrate that LT expressed only in G1 is capable of rescuing LT knockdown-induced growth suppression while LT expressed in S and G2/M phases fails to support proliferation of MCC cells. These results suggest that the crucial function of LT, which has been demonstrated to be inactivation of the cellular Retinoblastoma protein 1 (RB1) is only required to initiate S phase entry. View Full-Text
Keywords: Merkel cell polyomavirus; large T antigen; cell cycle; Merkel cell carcinoma Merkel cell polyomavirus; large T antigen; cell cycle; Merkel cell carcinoma
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MDPI and ACS Style

Houben, R.; Ebert, M.; Hesbacher, S.; Kervarrec, T.; Schrama, D. Merkel Cell Polyomavirus Large T Antigen is Dispensable in G2 and M-Phase to Promote Proliferation of Merkel Cell Carcinoma Cells. Viruses 2020, 12, 1162.

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