Asset Details
Do you wish to reserve the book?
Merkel Cell Polyomavirus Small T Antigen Is Oncogenic in Transgenic Mice
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Merkel Cell Polyomavirus Small T Antigen Is Oncogenic in Transgenic Mice
Do you wish to request the book?
Merkel Cell Polyomavirus Small T Antigen Is Oncogenic in Transgenic Mice
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Merkel Cell Polyomavirus Small T Antigen Is Oncogenic in Transgenic Mice
2015
Overview
Merkel cell carcinoma (MCC) is a rare and deadly neuroendocrine skin tumor frequently associated with clonal integration of a polyomavirus, Merkel cell polyomavirus (MCPyV), and MCC tumor cells express putative polyomavirus oncoprotein small T antigen (sTAg) and truncated large T antigen. Here, we show robust transforming activity of sTAg in vivo in a panel of transgenic mouse models. Epithelia of preterm sTAg-expressing embryos exhibited hyperplasia, impaired differentiation, increased proliferation, and apoptosis, and activation of a DNA damage response. Epithelial transformation did not require sTAg interaction with the protein phosphatase 2A protein complex, a tumor suppressor in some other polyomavirus transformation models, but was strictly dependent on a recently described sTAg domain that binds Fbxw7, the substrate-binding component of the Skp1/Cullin1/F-box protein ubiquitin ligase complex. Postnatal induction of sTAg using a Cre-inducible transgene also led to epithelial transformation with development of lesions resembling squamous cell carcinoma in situ and elevated expression of Fbxw7 target proteins. Our data establish that expression of MCPyV sTAg alone is sufficient for rapid neoplastic transformation in vivo, implicating sTAg as an oncogenic driver in MCC and perhaps other human malignancies. Moreover, the loss of transforming activity following mutation of the sTAg Fbxw7 binding domain identifies this domain as crucial for in vivo transformation.
Publisher
Elsevier Inc
Subject
/ Antigens, Viral, Tumor - immunology
/ Antigens, Viral, Tumor - physiology
/ Carcinoma, Merkel Cell - immunology
/ Carcinoma, Merkel Cell - pathology
/ Carcinoma, Merkel Cell - physiopathology
/ Cell Proliferation - physiology
/ Cell Transformation, Neoplastic - immunology
/ Cell Transformation, Neoplastic - pathology
/ Merkel cell polyomavirus - immunology
/ Mice
/ Polyomavirus Infections - immunology
