Abstract

In the last grant period this laboratory identified two of the cellular proteins bound by small and middle T antigens of polyoma virus as the 36kd catalytic and 63kd regulatory subunits of PP2A. We now propose to follow up our initial discovery by carrying out a careful genetic study of the structural requirements of the interaction. We will then proceed to use our mutants to attempt to gain insights into molecular details of the function of PP2A in vivo in both mammalian and insect systems. Finally we will attempt to push our understanding of the interaction to the atomic level via crystallography.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA050661-08
Application #
5207603
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Becker, Jürgen C; Stang, Andreas; Hausen, Axel Zur et al. (2018) Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC. Cancer Immunol Immunother 67:341-351
Becker, Jürgen C; Stang, Andreas; DeCaprio, James A et al. (2017) Merkel cell carcinoma. Nat Rev Dis Primers 3:17077
Denis, Deborah; Rouleau, Cecile; Schaffhausen, Brian S (2017) A Transformation-Defective Polyomavirus Middle T Antigen with a Novel Defect in PI3 Kinase Signaling. J Virol 91:
Starrett, Gabriel J; Marcelus, Christina; Cantalupo, Paul G et al. (2017) Merkel Cell Polyomavirus Exhibits Dominant Control of the Tumor Genome and Transcriptome in Virus-Associated Merkel Cell Carcinoma. MBio 8:
Cizmecioglu, Onur; Ni, Jing; Xie, Shaozhen et al. (2016) Rac1-mediated membrane raft localization of PI3K/p110? is required for its activation by GPCRs or PTEN loss. Elife 5:
Rouleau, Cecile; Pores Fernando, Arun T; Hwang, Justin H et al. (2016) Transformation by Polyomavirus Middle T Antigen Involves a Unique Bimodal Interaction with the Hippo Effector YAP. J Virol 90:7032-7045
Berrios, Christian; Jung, Joonil; Primi, Blake et al. (2015) Malawi polyomavirus is a prevalent human virus that interacts with known tumor suppressors. J Virol 89:857-62
Luo, Leo Y; Kim, Eejung; Cheung, Hiu Wing et al. (2015) The Tyrosine Kinase Adaptor Protein FRS2 Is Oncogenic and Amplified in High-Grade Serous Ovarian Cancer. Mol Cancer Res 13:502-9
Hettmer, Simone; Schinzel, Anna C; Tchessalova, Daria et al. (2015) Functional genomic screening reveals asparagine dependence as a metabolic vulnerability in sarcoma. Elife 4:
White, Elizabeth A; Kramer, Rebecca E; Hwang, Justin H et al. (2015) Papillomavirus E7 oncoproteins share functions with polyomavirus small T antigens. J Virol 89:2857-65

Showing the most recent 10 out of 147 publications