We have isolated mutations in the Drosophila ortholog of the human tumor susceptibility gene 101 (Tsg101) based upon their hyperplastic phenotype in the developing eye. A role for mammalian Tsg101 in tumorigenesis remains unresolved and it's mechanism in growth control poorly understood. Drosophila eye imaginal disc epithelia composed entirely of Tsg101 mutant cells continue to divide to form an undifferentiated tissue mass that exhibits defects in epithelial polarity. A similar phenotype is observed in imaginal discs that are mutant for one of the Drosophila neoplastic tumor suppressor class of genes (nTSGs). Each of the nTSGs encodes a protein whose localization and regulation are required for the establishment and maintenance of epithelial cell polarity. Thus, Tsg101 regulation may provide insight into the link between growth control and epithelial polarity, and the ultimate progression towards tumorigenesis. This research proposal will directly test 1) The major growth pathway that is deregulated by Tsg101 mutations and 2) The epistatic relationship between Tsg101 phenotypes (growth control and polarity defects) and the nTSGs. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM077898-02
Application #
7232333
Study Section
Special Emphasis Panel (ZRG1-F08-G (20))
Program Officer
Portnoy, Matthew
Project Start
2006-06-01
Project End
2008-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
2
Fiscal Year
2007
Total Cost
$48,796
Indirect Cost
Name
Emory University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Gilbert, M Melissa; Beam, Carolyn K; Robinson, Brian S et al. (2009) Genetic interactions between the Drosophila tumor suppressor gene ept and the stat92E transcription factor. PLoS One 4:e7083
Gilbert, M Melissa; Robinson, Brian S; Moberg, Kenneth H (2009) Functional interactions between the erupted/tsg101 growth suppressor gene and the DaPKC and rbf1 genes in Drosophila imaginal disc tumors. PLoS One 4:e7039