Abstract

Studies will be carried out on the mechanisms by which polyoma virus's middle T antigen transforms cultured fibroblasts. Since middle T has no known biochemical activity it is thought to transform by binding to and modulating the activities of certain key cellular proteins. Hence these studies will focus on two complementary aspects of middle T antigen: First a series of genetic studies will be carried out on middle T. These will be aimed at determining how many key sites on the molecule are important to transformation. As sites are defined they will be tested to see into which complementation group they fall. Additional genetic studies will be carried out on two known motifs as well. Biochemical studies will focus on Mtag's interaction with the Pi3' kinase and the 27/29kDa cellular proteins which are bound by Mtag and on identifying cellular proteins which are phosphorylated on tyrosine in Mtag transformed cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA030002-18
Application #
2871674
Study Section
Special Emphasis Panel (NSS)
Program Officer
Read-Connole, Elizabeth Lee
Project Start
1982-02-01
Project End
2000-01-31
Budget Start
1999-02-01
Budget End
2000-01-31
Support Year
18
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

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:
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
Utermark, Tamara; Rao, Trisha; Cheng, Hailing et al. (2012) The p110ýý and p110ýý isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis. Genes Dev 26:1573-86
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
Ilic, Nina; Utermark, Tamara; Widlund, Hans R et al. (2011) PI3K-targeted therapy can be evaded by gene amplification along the MYC-eukaryotic translation initiation factor 4E (eIF4E) axis. Proc Natl Acad Sci U S A 108:E699-708
Hein, Jennifer; Boichuk, Sergei; Wu, Jiaping et al. (2009) Simian virus 40 large T antigen disrupts genome integrity and activates a DNA damage response via Bub1 binding. J Virol 83:117-27

Showing the most recent 10 out of 55 publications