A universal challenge faced by all living organisms is to identify and then attempt to counteract the deleterious effects of environmental stresses. Whether multicellular or unicellular, all organisms have evolved mechanisms to deal with such molecular insults. Indeed the fundamental mechanisms for responding to such agents as ionizing radiation, oxidative stress, mutagenic and toxic small molecules, nutrient deprivation and temperature extremes (heat shock) have been highly and evolutionarily conserved at the molecular level. A cardinal feature of all of these molecular-cellular protective mechanisms is the induction of the transcription of certain cellular genes encoding proteins that confer stress-protective properties. Concomitantly, transcription of genes encoding proteins (and RNAs) that lack protective cellular/molecular effects is repressed. These critical transcriptional responses are all mediated through the actions of a handful of distinct transcriptional activator and repressor proteins. In this study, the investigators propose to use state-of-the-art multidimensional tandem mass spectrometry methods to identify and characterize the protein-protein regulatory networks connecting the environment with key conserved transcription factors known to drive the gene-level protective changes in cellular RNA synthesis. The studies will initially focus on the genetically tractable and simple eukaryote Baker's yeast (Saccharomyces cerevisiae). However, in the latter phase of this project, they will apply the knowledge gained in the unicellular yeast model system to human cells.
Farley, Adam R; Powell, David W; Weaver, Connie M et al. (2011) Assessing the components of the eIF3 complex and their phosphorylation status. J Proteome Res 10:1481-94 |
Arnett, Diana R; Jennings, Jennifer L; Tabb, David L et al. (2008) A proteomics analysis of yeast Mot1p protein-protein associations: insights into mechanism. Mol Cell Proteomics 7:2090-106 |
Burg, John S; Powell, David W; Chai, Raymond et al. (2008) Insig regulates HMG-CoA reductase by controlling enzyme phosphorylation in fission yeast. Cell Metab 8:522-31 |
Osipovich, Anna B; Jennings, Jennifer L; Lin, Qing et al. (2008) Dyggve-Melchior-Clausen syndrome: chondrodysplasia resulting from defects in intracellular vesicle traffic. Proc Natl Acad Sci U S A 105:16171-6 |
Gerbasi, Vincent R; Link, Andrew J (2007) The myotonic dystrophy type 2 protein ZNF9 is part of an ITAF complex that promotes cap-independent translation. Mol Cell Proteomics 6:1049-58 |
Venkov, Christo D; Link, Andrew J; Jennings, Jennifer L et al. (2007) A proximal activator of transcription in epithelial-mesenchymal transition. J Clin Invest 117:482-91 |
Bozulic, Larry D; Malik, Mohammad T; Powell, David W et al. (2007) Plasma membrane Ca(2+) -ATPase associates with CLP36, alpha-actinin and actin in human platelets. Thromb Haemost 97:587-97 |
Hughes, Adam L; Powell, David W; Bard, Martin et al. (2007) Dap1/PGRMC1 binds and regulates cytochrome P450 enzymes. Cell Metab 5:143-9 |
Teng, Yingqi; Zeisberg, Michael; Kalluri, Raghu (2007) Transcriptional regulation of epithelial-mesenchymal transition. J Clin Invest 117:304-6 |
Yoon, Hyun-Joo; Feoktistova, Anna; Chen, Jun-Song et al. (2006) Role of Hcn1 and its phosphorylation in fission yeast anaphase-promoting complex/cyclosome function. J Biol Chem 281:32284-93 |
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