Protein chaperones and stress response in saccharomyces cerevisiae
The heat shock response is highly conserved in all kingdoms, making it one of the most ancient cellular regulatory systems. We have two primary interests, 1) how heat shock is sensed and transduced to yield a genome-wide transcriptional response, and 2) how protein chaperones, including the Hsp70, Hsp90 and the Hsp110 groups, function collaboratively within the cell during normal growth and during adaptation to environmental stress.
The baker's yeast, Saccharomyces cerevisiae, is an ideal microbial model system in which to investigate these questions, due to its facile genetics, genomics and ease of manipulation. These studies will directly impact our understanding of how human cells respond to pathophysiological states such as cancer and anoxia which strongly induce a heat shock response. In addition, there is growing evidence that the amyloid diseases of protein misfolding, including prion- based maladies such as Creutzfelt-Jakob (mad cow), and other triplet- repeat type diseases including Alzheimer's, Parkinson's, and Hunginton's, are intimately linked to protein chaperone expression and function. |
Schuermann JP, Jiang J, Cuellar J, Llorca O, Wang L, Gimenez LE, Jin S, Taylor AB, Demeler B, Morano KA, Hart PJ, Valpuesta JM, Lafer EM, Sousa R. Structure of the Hsp110:Hsc70 nucleotide exchange machine. Mol Cell. 31:232-243, 2008.
Shaner L, Gibney PA, Morano KA. The Hsp110 protein chaperone Sse1 is required for yeast cell wall integrity and morphogenesis. Curr Genet. 54:1-11, 2008.
Gibney PA, Fries T, Bailer SM, Morano KA. Rtr1 is the Saccharomyces cerevisiae homolog of a novel family of RNA polymerase II-binding proteins. Eukaryot Cell. 7:938-948, 2008.
Trott A, West JD, Klai? L, Westerheide SD, Silverman RB, Morimoto RI, Morano KA. Activation of heat shock and antioxidant responses by the natural product celastrol: transcriptional signatures of a thiol-targeted molecule. Mol Biol Cell. 19:1104-1112, 2008.
Fan Q, Park KW, Du Z, Morano KA, Li L. The role of Sse1 in the de novo formation and variant determination of the [PSI+] prion. Genetics. 177:1583-1593, 2007.
Morano KA. New tricks for an old dog: the evolving world of Hsp70. Ann N Y Acad Sci. 1113:1-14, 2007.
Shaner L, Morano KA. All in the family: atypical Hsp70 chaperones are conserved modulators of Hsp70 activity. Cell Stress Chaperones. 12:1-8, 2007.
Shaner L, Sousa R, Morano KA. Characterization of Hsp70 binding and nucleotide exchange by the yeast Hsp110 chaperone Sse1. Biochemistry. 45:15075-15084, 2006.
Shaner L, Wegele H, Buchner J, and Morano KA The yeast Hsp110
Sse1 functionally interacts with the Hsp70 chaperones Ssa and Ssb. J Biol Chem, 280, 41262-41269, 2005.
Trott, A., Shaner, L. and Morano, K.A., The molecular chaperone Sse1 and the growth control protein kinase Sch9 collaborate to regulate protein kinase A activity in Saccharomyces cerevisiae.
Genetics, 170:1009-1021, 2005.
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Department of Microbiology and Molecular Genetics