Abstract

The long range goal of this project is to characterize the mechanism(s) by which gene expression is regulated in eukaryotic organisms using the Saccharomyces yeast as model eukaryotes and the fermenatation of maltose as a model regulated system. The fermentation of maltose in Saccharomyces utilizes two enzyme functions: maltose permease an maltase. The expression of the structural genes encoding these enzyme is induced by maltose and repressed by glucose. In order to ferment maltose a strain must carry any one of five unlinked MAL loci. We have extensivley characterized the MAL6 locus and shown it to encode three genes: MAL61. encoding maltose permease; MAL62. encoding maltase; and MAL63, encoding a positive regulatory function controlling the expression of both structural genes. In this proposal we plan to: (1) Complete the transcriptional analysis of the MAL6 locus. (2) Define the upstream sequences controlling the expression of the structural genes, MAL61, and MAL62. (3) Characterize the functinal domains of the MAL63 gene product, particularly its DNA binding activity. (4) Analyze the MAL64-constitutive mutations and determine the mechanism of mutation ativating this MAL64 gene product in the constitutive mutations. (5) Identify new genes encoding products which interact with the MAL61 -MAL62 controlling sequences or with the MAL63 gene product and thus also involved in the regulation of gene expression of these structural genes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM028216-13
Application #
3275499
Study Section
Genetics Study Section (GEN)
Project Start
1980-07-01
Project End
1992-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
13
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Queens College
Department
Type
Schools of Arts and Sciences
DUNS #
City
Flushing
State
NY
Country
United States
Zip Code
11367

  Publications

Ran, Fulai; Gadura, Nidhi; Michels, Corinne A (2010) Hsp90 cochaperone Aha1 is a negative regulator of the Saccharomyces MAL activator and acts early in the chaperone activation pathway. J Biol Chem 285:13850-62
Ran, Fulai; Bali, Mehtap; Michels, Corinne A (2008) Hsp90/Hsp70 chaperone machine regulation of the Saccharomyces MAL-activator as determined in vivo using noninducible and constitutive mutant alleles. Genetics 179:331-43
Gadura, Nidhi; Michels, Corinne A (2006) Sequences in the N-terminal cytoplasmic domain of Saccharomyces cerevisiae maltose permease are required for vacuolar degradation but not glucose-induced internalization. Curr Genet 50:101-14
Gadura, Nidhi; Robinson, Lucy C; Michels, Corinne A (2006) Glc7-Reg1 phosphatase signals to Yck1,2 casein kinase 1 to regulate transport activity and glucose-induced inactivation of Saccharomyces maltose permease. Genetics 172:1427-39
Wang, Xin; Michels, Corinne A (2004) Mutations in SIN4 and RGR1 cause constitutive expression of MAL structural genes in Saccharomyces cerevisiae. Genetics 168:747-57
Bali, Mehtap; Zhang, Bin; Morano, Kevin A et al. (2003) The Hsp90 molecular chaperone complex regulates maltose induction and stability of the Saccharomyces MAL gene transcription activator Mal63p. J Biol Chem 278:47441-8
Danzi, Sara E; Bali, Mehtap; Michels, Corinne A (2003) Clustered-charge to alanine scanning mutagenesis of the Mal63 MAL-activator C-terminal regulatory domain. Curr Genet 44:173-83
Wang, Xin; Bali, Mehtap; Medintz, Igor et al. (2002) Intracellular maltose is sufficient to induce MAL gene expression in Saccharomyces cerevisiae. Eukaryot Cell 1:696-703
Jiang, H; Tatchell, K; Liu, S et al. (2000) Protein phosphatase type-1 regulatory subunits Reg1p and Reg2p act as signal transducers in the glucose-induced inactivation of maltose permease in Saccharomyces cerevisiae. Mol Gen Genet 263:411-22
Hu, Z; Yue, Y; Jiang, H et al. (2000) Analysis of the mechanism by which glucose inhibits maltose induction of MAL gene expression in Saccharomyces. Genetics 154:121-32

Showing the most recent 10 out of 29 publications