Abstract

The SKVs are a group of avian retroviruses possessing the common oncogene, ski. The present studies will probe the activity of the ski gene by examining the phenotype of SKV-infected chicken and quail embryo cells. A nondefective SKV, constructed from molecularly cloned DNAs will be the starting material for the construction of mutant viruses which will be used to dissect the biological activities of the ski gene and the biochemical properties of its encoded protein. Related techniques will be employed to generate recombinant viral genomes using fragments of the cellular proto-oncogene c-ski to replace deleted portions of the viral homolog. The goal of these studies is to identify the regions of the viral gene that are responsible for its transforming capacity and to determine which properties and functions of the gene relate to its activation as an oncogene. Additional studies will be performed to determine the structure and study the expression of c-ski. These studies will explore its expression with respect to the cell division cycle and during chicken embryogenesis. The possible involvement of ski in human malignancy will be studied by cloning the human homolog of ski and examining the possible rearrangement or amplification of the gene in DNAs from human tumors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA043600-03
Application #
3185832
Study Section
Experimental Virology Study Section (EVR)
Project Start
1986-03-01
Project End
1989-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Cincinnati
Department
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221

  Publications

Zhang, Hong; Stavnezer, Ed (2009) Ski regulates muscle terminal differentiation by transcriptional activation of Myog in a complex with Six1 and Eya3. J Biol Chem 284:2867-79
Atanasoski, Suzana; Notterpek, Lucia; Lee, Hye-Youn et al. (2004) The protooncogene Ski controls Schwann cell proliferation and myelination. Neuron 43:499-511
Johnson, Michael; Morris, Shannon; Chen, Aiping et al. (2004) Selection of functional mutations in the U5-IR stem and loop regions of the Rous sarcoma virus genome. BMC Biol 2:8
Chen, Dahu; Xu, Weidong; Bales, Elise et al. (2003) SKI activates Wnt/beta-catenin signaling in human melanoma. Cancer Res 63:6626-34
Morris, Shannon; Johnson, Michael; Stavnezer, Ed et al. (2002) Replication of avian sarcoma virus in vivo requires an interaction between the viral RNA and the TpsiC loop of the tRNA(Trp) primer. J Virol 76:7571-7
Xu, W; Angelis, K; Danielpour, D et al. (2000) Ski acts as a co-repressor with Smad2 and Smad3 to regulate the response to type beta transforming growth factor. Proc Natl Acad Sci U S A 97:5924-9
Nicol, R; Zheng, G; Sutrave, P et al. (1999) Association of specific DNA binding and transcriptional repression with the transforming and myogenic activities of c-Ski. Cell Growth Differ 10:243-54
Cohen, S B; Zheng, G; Heyman, H C et al. (1999) Heterodimers of the SnoN and Ski oncoproteins form preferentially over homodimers and are more potent transforming agents. Nucleic Acids Res 27:1006-14
Nicol, R; Stavnezer, E (1998) Transcriptional repression by v-Ski and c-Ski mediated by a specific DNA binding site. J Biol Chem 273:3588-97
Cohen, S B; Nicol, R; Stavnezer, E (1998) A domain necessary for the transforming activity of SnoN is required for specific DNA binding, transcriptional repression and interaction with TAF(II)110. Oncogene 17:2505-13

Showing the most recent 10 out of 22 publications