Hesbacher, Sonja and Pfitzer, Lisa and Wiedorfer, Katharina and Angermeyer, Sabrina and Borst, Andreas and Haferkamp, Sebastian and Scholz, Claus-Juergen and Wobser, Marion and Schrama, David and Houben, Roland (2016) RB1 is the crucial target of the Merkel cell polyomavirus Large T antigen in Merkel cell carcinoma cells. ONCOTARGET, 7 (22). pp. 32956-32968. ISSN 1949-2553,
Full text not available from this repository. (Request a copy)Abstract
The pocket protein (PP) family consists of the three members RB1, p107 and p130 all possessing tumor suppressive properties. Indeed, the PPs jointly control the G1/S transition mainly by inhibiting E2F transcription factors. Notably, several viral oncoproteins are capable of binding and inhibiting PPs. Merkel cell polyomavirus (MCPyV) is considered as etiological factor for Merkel cell carcinoma (MCC) with expression of the viral Large T antigen (LT) harboring an intact PP binding domain being required for proliferation of most MCC cells. Therefore, we analyzed the interaction of MCPyV-LT with the PPs. Co-IP experiments indicate that MCPyV-LT binds potently only to RB1. Moreover, MCPyV-LT knockdown-induced growth arrest in MCC cells can be rescued by knockdown of RB1, but not by p107 or p130 knockdown. Accordingly, cell cycle arrest and E2F target gene repression mediated by the single PPs can only in the case of RB1 be significantly reverted by MCPyV-LT expression. Moreover, data from an MCC patient indicate that loss of RB1 rendered the MCPyV-positive MCC cells LT independent. Thus, our results suggest that RB1 is the dominant tumor suppressor PP in MCC, and that inactivation of RB1 by MCPyV-LT is largely sufficient for its growth supporting function in established MCPyV-positive MCC cells.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RETINOBLASTOMA FAMILY PROTEINS; TUMOR-SUPPRESSOR PROTEINS; PRB-RELATED PROTEINS; REQUIRE EXPRESSION; GENE-EXPRESSION; TISSUE CULTURE; CYCLE CONTROL; J DOMAIN; MICE; TRANSFORMATION; Merkel cell carcinoma; polyomavirus; Large T antigen; retinoblastoma protein; viral carcinogenesis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Mar 2019 14:07 |
| Last Modified: | 25 Mar 2019 14:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2916 |
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