Abstract

The thrust of this proposal is to continue and expand an analysis of eukaryotic transcriptional activation at the molecular level. The model system employed is the CYC1 gene (iso-1-cytochrome c) of the yeast Saccharomyces cerevisiae. The transcriptional activators that regulate this gene, HAP1, HAP2, HAP3, and HAP4, have many features in common with activators from higher cells. These features include mechanisms of activation the transcriptional machinery, and regulation by small effectors and by post-translational modification. In higher cells, transcriptional activators play key roles in growth control and cancer (several oncogenes are activators of transcription), and are involved in key decisions in embryonic development.
The specific aims of the proposal include studies of the yeast activators using a combined approach of biochemistry, molecular biology, molecular genetics, and classical yeast genetics. Further, certain experiments will provide and entree' into studies of related molecule in animal cells. It is hoped that these studies will contribute to a coherent and unified understanding of how eukaryotic activators work and how they are regulated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM030454-10
Application #
3278230
Study Section
Molecular Biology Study Section (MBY)
Project Start
1982-05-01
Project End
1995-04-30
Budget Start
1991-05-01
Budget End
1992-04-30
Support Year
10
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

McNabb, D S; Pak, S M; Guarente, L (1997) Cassette for the generation of sequential gene disruptions in the yeast Schizosaccharomyces pombe. Biotechniques 22:1134-9
McNabb, D S; Tseng, K A; Guarente, L (1997) The Saccharomyces cerevisiae Hap5p homolog from fission yeast reveals two conserved domains that are essential for assembly of heterotetrameric CCAAT-binding factor. Mol Cell Biol 17:7008-18
Zhang, L; Guarente, L (1995) Heme binds to a short sequence that serves a regulatory function in diverse proteins. EMBO J 14:313-20
Haldi, M L; Guarente, L (1995) Multiple domains mediate heme control of the yeast activator HAP1. Mol Gen Genet 248:229-35
McNabb, D S; Xing, Y; Guarente, L (1995) Cloning of yeast HAP5: a novel subunit of a heterotrimeric complex required for CCAAT binding. Genes Dev 9:47-58
Zhang, L; Guarente, L (1994) HAP1 is nuclear but is bound to a cellular factor in the absence of heme. J Biol Chem 269:14643-7
Zhang, L; Guarente, L (1994) Evidence that TUP1/SSN6 has a positive effect on the activity of the yeast activator HAP1. Genetics 136:813-7
Xing, Y; Zhang, S; Olesen, J T et al. (1994) Subunit interaction in the CCAAT-binding heteromeric complex is mediated by a very short alpha-helix in HAP2. Proc Natl Acad Sci U S A 91:3009-13
Kennedy, B K; Austriaco Jr, N R; Guarente, L (1994) Daughter cells of Saccharomyces cerevisiae from old mothers display a reduced life span. J Cell Biol 127:1985-93
Zhang, L; Guarente, L (1994) The yeast activator HAP1--a GAL4 family member--binds DNA in a directly repeated orientation. Genes Dev 8:2110-9

Showing the most recent 10 out of 35 publications