This grant is designed to study the mechanisms underlying the effects of polyoma virus' Middle T (MT) antigen and SV40 virus' small t (st) antigen. Recent experiments have greatly increased interest in st. It has been found to play a key role in transforming telomerase-immortalized human epithelial cells in the Weinberg system and in selectively inducing apoptosis in tumor, but not normal, cell lines. Both effects of st are believed to arise from its interaction with a protein phosphatase, PP2A. The experiments in this grant will examine the molecular details by which st selectively inhibits certain isoforms of PP2A by displacing particular B-type subunits. Understanding these details may lead directly to cancer therapy. Similarly the experiments in the grant will study the mechanisms by which MT transforms human epithelial cells. In the last grant period we discovered a new class of mutants in MT that suggests the existence of a new MT binding protein hypothesized to be important in transformation. By using newly developed protocols for isolating all proteins which interact with a target protein, we hope to identify the hypothetical Protein X. Subsequent experiments will test the importance of Protein X in transformation. Once again it is proposed that understanding these mechanisms of MT-mediated transformation may lead to potential therapies for human cancers. ? ? ?

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Experimental Virology Study Section (EVR)
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Blair, Donald G
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Dana-Farber Cancer Institute
United States
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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
Hashim, D; Sartori, S; Brennan, P et al. (2016) The role of oral hygiene in head and neck cancer: results from International Head and Neck Cancer Epidemiology (INHANCE) consortium. Ann Oncol 27:1619-25
Pores Fernando, A T; Andrabi, S; Cizmecioglu, O et al. (2015) Polyoma small T antigen triggers cell death via mitotic catastrophe. Oncogene 34:2483-92
Utermark, Tamara; Schmit, Fabienne; Lee, Sang Hyun et al. (2014) The phosphatidylinositol 3-kinase (PI3K) isoform dependence of tumor formation is determined by the genetic mode of PI3K pathway activation rather than by tissue type. J Virol 88:10673-9
Hwang, Justin H; Pores Fernando, Arun T; Faure, Nathalie et al. (2014) Polyomavirus small T antigen interacts with yes-associated protein to regulate cell survival and differentiation. J Virol 88:12055-64
Schmit, Fabienne; Utermark, Tamara; Zhang, Sen et al. (2014) PI3K isoform dependence of PTEN-deficient tumors can be altered by the genetic context. Proc Natl Acad Sci U S A 111:6395-400
Jia, Shidong; Gao, Xueliang; Lee, Sang Hyun et al. (2013) Opposing effects of androgen deprivation and targeted therapy on prostate cancer prevention. Cancer Discov 3:44-51
Ni, Jing; Liu, Qingsong; Xie, Shaozhen et al. (2012) Functional characterization of an isoform-selective inhibitor of PI3K-p110? as a potential anticancer agent. Cancer Discov 2:425-33
Pugh, Trevor J; Weeraratne, Shyamal Dilhan; Archer, Tenley C et al. (2012) Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature 488:106-10

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