| Title: | The Hsp90-dependent proteome is conserved and enriched for hub proteins with high levels of protein-protein connectivity |
| Author(s): | Gopinath RK; You ST; Chien KY; Swamy KB; Yu JS; Schuyler SC; Leu JY; |
| Address: | "Molecular and Cell Biology, Taiwan International Graduate Program, Graduate Institute of Life Sciences, National Defense Medical Center and Academia Sinica Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan schuyler@mail.cgu.edu.tw jleu@imb.sinica.edu.tw. Molecular Medicine Research Center, Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan schuyler@mail.cgu.edu.tw jleu@imb.sinica.edu.tw. Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan. Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan. Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan schuyler@mail.cgu.edu.tw jleu@imb.sinica.edu.tw. Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan schuyler@mail.cgu.edu.tw jleu@imb.sinica.edu.tw" |
| ISSN/ISBN: | 1759-6653 (Electronic) 1759-6653 (Linking) |
| Abstract: | "Hsp90 is one of the most abundant and conserved proteins in the cell. Reduced levels or activity of Hsp90 causes defects in many cellular processes and also reveals genetic and nongenetic variation within a population. Despite information about Hsp90 protein-protein interactions, a global view of the Hsp90-regulated proteome in yeast is unavailable. To investigate the degree of dependency of individual yeast proteins on Hsp90, we used the 'stable isotope labeling by amino acids in cell culture' method coupled with mass spectrometry to quantify around 4,000 proteins in low-Hsp90 cells. We observed that 904 proteins changed in their abundance by more than 1.5-fold. When compared with the transcriptome of the same population of cells, two-thirds of the misregulated proteins were observed to be affected posttranscriptionally, of which the majority were downregulated. Further analyses indicated that the downregulated proteins are highly conserved and assume central roles in cellular networks with a high number of protein interacting partners, suggesting that Hsp90 buffers genetic and nongenetic variation through regulating protein network hubs. The downregulated proteins were enriched for essential proteins previously not known to be Hsp90-dependent. Finally, we observed that downregulation of transcription factors and mating pathway components by attenuating Hsp90 function led to decreased target gene expression and pheromone response, respectively, providing a direct link between observed proteome regulation and cellular phenotypes" |
| Keywords: | Animals Genomics/methods HSP90 Heat-Shock Proteins/genetics/*metabolism Humans Protein Binding Proteomics/methods Saccharomyces cerevisiae/genetics/metabolism genetic buffering molecular chaperone protein network yeast genomics yeast proteomics; |
| Notes: | "MedlineGopinath, Rajaneesh Karimpurath You, Shu-Ting Chien, Kun-Yi Swamy, Krishna B S Yu, Jau-Song Schuyler, Scott C Leu, Jun-Yi eng Research Support, Non-U.S. Gov't England 2014/10/16 Genome Biol Evol. 2014 Oct 13; 6(10):2851-65. doi: 10.1093/gbe/evu226" |
