The fission yeast Schizosaccharomyces pombe has been utilized as a model system to study mammalian and viral gene regulation. The early adenovirus E2-promoter, which contains two overlapping promoters has been shown to be efficiently expressed in S. pombe. Mutations within the cis- acting control elements of the E2 promoter revealed that S. pombe has a cellular counterpart to the mammalian transcription factor E2F. In mammalian cells, E2F plays an important role in the G1 and S phase of the mammalian cell cycle by regulating genes that are essential for the control of cell cycle. Yeast replicating and integrating vectors have been developed to isolate mammalian cDNA clones encoding transcription factors by genetic complementation into S. pombe. These vectors have been used to select cDNA clones that encode transcription factors which increase transcription from the promoter of human immunodeficiency virus 1 (HIV-1) and the promoter of the human low density lipoprotein receptor (LDLR). The study of HIV-gag mRNA revealed the inability of the viral Rev protein to enhance the transport of gag mRNA into the cytoplasm in S. pombe. An in situ hybridization method was developed to screen temperature- sensitive (ts) mutants for growth of S. pombe which are unable to transport mRNA to the cytoplasm at nonpermissive temperature. Two (ts) mutants for mRNA transport have been identified which accumulate mRNA in the nucleus at high temperature. These mutants are being used to study the Rev-dependent transport of HIV-1 mRNA.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP005643-03
Application #
3838435
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code