title: Emerging differential roles of the pRb tumor suppressor in trichodysplasia spinulosa-associated polyomavirus and Merkel cell polyomavirus pathogeneses.
abstract: BACKGROUND
  Merkel cell carcinoma (MCC) and trichodysplasia spinulosa (TS) are two proliferative cutaneous diseases caused by the Merkel cell polyomavirus (MCPyV) and trichodysplasia spinulosa-associated polyomavirus (TSPyV) respectively. Recently, studies have elucidated a key role of the small tumor (sT) antigen in the proliferative pathogenic mechanisms of MCPyV and likely TSPyV. While both sT antigens have demonstrated a capacity in regulating cellular pathways, it remains unknown whether MCPyV and TSPyV sT antigens contribute similarly or differentially to cell proliferation.
  
  
  OBJECTIVE
  The present study aims to explore the proliferative potential of MCPyV and TSPyV sT antigens by investigating their regulatory effects on the retinoblastoma protein (pRb) tumor suppressor.
  
  
  METHODS
  Inducible cell lines expressing MCPyV sT or TSPyV sT were created using a lentiviral packaging system. Cellular proteins were extracted and subjected to SDS-PAGE followed by Western blot detection and densitometric analysis.
  
  
  RESULTS
  Expression of TSPyV sT markedly enhanced the phosphorylation of pRb in Western blot experiments. In contrast, expression of MCPyV sT did not alter pRb phosphorylation under the same experimental conditions. Densitometric analysis revealed that TSPyV sT antigen expression nearly doubled the ratio of phosphorylated to total pRb (P<0.001, Student's T-test), while MCPyV sT antigen expression did not cause significant change in pRb phosphorylation status.
  
  
  CONCLUSIONS
  Given that hyperphosphorylation of pRb is associated with dysregulation of the cell cycle, S-phase induction, and increased cell proliferation, our findings support an important role of TSPyV-mediated pRb deactivation in the development of TS. The observation that the pRb tumor suppressor is inactivated by TSPyV sT but not MCPyV sT provides further insights into the distinct pathobiological mechanisms of MCC and TS.
authors.affiliation: Department of Dermatology, University of Texas Medical School at Houston, TX 77030, United States; Baylor College of Medicine, Houston, TX 77030, United States.
authors.forename: Julie H
authors.initials: JH
authors.lastname: Wu
authors.affiliation: Department of Dermatology, University of Texas Medical School at Houston, TX 77030, United States.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Simonette
authors.affiliation: Department of Dermatology, University of Texas Medical School at Houston, TX 77030, United States; Baylor College of Medicine, Houston, TX 77030, United States.
authors.forename: Harrison P
authors.initials: HP
authors.lastname: Nguyen
authors.affiliation: Department of Dermatology, University of Texas Medical School at Houston, TX 77030, United States.
authors.forename: Hung Q
authors.initials: HQ
authors.lastname: Doan
authors.affiliation: Department of Dermatology, University of Texas Medical School at Houston, TX 77030, United States.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Rady
authors.affiliation: Department of Dermatology, University of Texas Medical School at Houston, TX 77030, United States. Electronic address: styring@ccstexas.com.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Tyring
mesh_terms: D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000502:physiology*; D015266:Carcinoma, Merkel Cell / Q000503:physiopathology / Q000821:virology*; D002453:Cell Cycle; D002460:Cell Line; D004279:DNA, Viral; D057809:HEK293 Cells; D006201:Hair Diseases / Q000821:virology*; D006801:Humans; D007057:Ichthyosis / Q000821:virology*; D059965:Merkel cell polyomavirus / Q000235:genetics / Q000472:pathogenicity*; D010766:Phosphorylation; D027382:Polyomaviridae / Q000235:genetics / Q000472:pathogenicity*; D027601:Polyomavirus Infections / Q000150:complications / Q000821:virology; D016160:Retinoblastoma Protein / Q000378:metabolism*; D012878:Skin Neoplasms
chemical_list: D000952:Antigens, Polyomavirus Transforming; D004279:DNA, Viral; D016160:Retinoblastoma Protein
keywords: MCPyV; Merkel cell carcinoma; Small T antigen; TSPyV; Trichodysplasia spinulosa; pRb