@article{RitterFanPaulsonetal.2016,
  author    = {Ritter, Cathrin and Fan, Kaiji and Paulson, Kelly G. and Nghiem, Paul and Schrama, David and Becker, J{\"u}rgen C.},
  title     = {Reversal of epigenetic silencing of MHC class I chain-related protein A and B improves immune recognition of Merkel cell carcinoma},
  series = {Scientific Reports},
  journal   = {Scientific Reports},
  number    = {21678},
  edition   = {6},
  doi       = {10.1038/srep21678},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167992},
  year      = {2016},
  abstract  = {Merkel cell carcinoma (MCC) is a virally associated cancer characterized by its aggressive behavior and strong immunogenicity. Both viral infection and malignant transformation induce expression of MHC class I chain-related protein (MIC) A and B, which signal stress to cells of the immune system via Natural Killer group 2D (NKG2D) resulting in elimination of target cells. However, despite transformation and the continued presence of virally-encoded proteins, MICs are only expressed in a minority of MCC tumors in situ and are completely absent on MCC cell lines in vitro. This lack of MIC expression was due to epigenetic silencing via MIC promoter hypo-acetylation; indeed, MIC expression was re-induced by pharmacological inhibition of histone deacetylases (HDACs) both in vitro and in vivo. This re-induction of MICs rendered MCC cells more sensitive to immune-mediated lysis. Thus, epigenetic silencing of MICs is an important immune escape mechanism of MCCs.},
  language  = {en}
}
@article{HesbacherPfitzerWiedorferetal.2016,
  author    = {Hesbacher, Sonja and Pfitzer, Lisa and Wiedorfer, Katharina and Angermeyer, Sabrina and Borst, Andreas and Haferkamp, Sebastian and Scholz, Claus-J{\"u}rgen and Wobser, Marion and Schrama, David and Houben, Roland},
  title     = {RB1 is the crucial target of the Merkel cell polyomavirus Large T antigen in Merkel cell carcinoma cells},
  series = {Oncotarget},
  volume    = {7},
  journal   = {Oncotarget},
  number    = {22},
  doi       = {10.18632/oncotarget.8793},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177858},
  pages     = {32956-32968},
  year      = {2016},
  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.},
  language  = {en}
}