Abstract

The objective is to understand how retroviruses lacking an oncogene cause tissue-specific neoplastic disease. The role of the LTR in this process is well-known.One important region within the LTR is the DEN (downstream of enhancer) but its role in pathogenesis is not understood. This element is unique in its ability to induce transcription in activated T cells. Work proposed will first identify the elements within DEN that confer transcriptional activity in activated T cells.Proteins that bind to this region will be identified and the importance of these interactions will be tested using transient expression assays.
In aim 2 mutants with large effects identified in Aim 1 will be tested for leukemogenicity in mice.
In aim 3, factors that bind to DEN in nonactivated T cells will be identified to test the idea that binding of both constitutive and induced (present in activated T cells only) are important for function of the DEN. Identifying these factors and elucidating their role in pathogenesis should contribute to a broader understanding of gene regulation in T cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA044166-09A1
Application #
2091388
Study Section
Experimental Virology Study Section (EVR)
Project Start
1979-04-01
Project End
1995-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
9
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Yoshimura, Fayth K; Luo, Xixia; Zhao, Xiaoqing et al. (2008) Up-regulation of a cellular protein at the translational level by a retrovirus. Proc Natl Acad Sci U S A 105:5543-8
Zhao, Xiaoqing; Yoshimura, Fayth K (2008) Expression of murine leukemia virus envelope protein is sufficient for the induction of apoptosis. J Virol 82:2586-9
Yoshimura, Fayth K; Luo, Xixia (2007) Induction of endoplasmic reticulum stress in thymic lymphocytes by the envelope precursor polyprotein of a murine leukemia virus during the preleukemic period. J Virol 81:4374-7
Nanua, Suparna; Yoshimura, Fayth K (2004) Mink epithelial cell killing by pathogenic murine leukemia viruses involves endoplasmic reticulum stress. J Virol 78:12071-4
Nanua, Suparna; Yoshimura, Fayth K (2004) Differential cell killing by lymphomagenic murine leukemia viruses occurs independently of p53 activation and mitochondrial damage. J Virol 78:5088-96
Yoshimura, F K; Wang, T (2001) Role of the LTR region between the enhancer and promoter in mink cell focus-forming murine leukemia virus pathogenesis. Virology 283:121-31
Yoshimura, F K; Wang, T; Nanua, S (2001) Mink cell focus-forming murine leukemia virus killing of mink cells involves apoptosis and superinfection. J Virol 75:6007-15
Yoshimura, F K; Wang, T; Yu, F et al. (2000) Mink cell focus-forming murine leukemia virus infection induces apoptosis of thymic lymphocytes. J Virol 74:8119-26
Yoshimura, F K; Wang, T; Cankovic, M (1999) Sequences between the enhancer and promoter in the long terminal repeat affect murine leukemia virus pathogenicity and replication in the thymus. J Virol 73:4890-8
Chen, H; Yoshimura, F K (1998) Spacing between the enhancer and promoter of the long terminal repeat of a murine leukaemia retrovirus is required for transcriptional activation in T cells. J Gen Virol 79 ( Pt 5):1101-4

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