Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90 Journal Article
| Authors: | Moulick, K.; Ahn, J. H.; Zong, H.; Rodina, A.; Cerchietti, L.; Gomes DaGama, E. M.; Caldas-Lopes, E.; Beebe, K.; Perna, F.; Hatzi, K.; Vu, L. P.; Zhao, X.; Zatorska, D.; Taldone, T.; Smith-Jones, P.; Alpaugh, M.; Gross, S. S.; Pillarsetty, N.; Ku, T.; Lewis, J. S.; Larson, S. M.; Levine, R.; Erdjument-Bromage, H.; Guzman, M. L.; Nimer, S. D.; Melnick, A.; Neckers, L.; Chiosis, G. |
| Article Title: | Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90 |
| Abstract: | Most cancers are characterized by multiple molecular alterations, but identification of the key proteins involved in these signaling pathways is currently beyond reach. We show that the inhibitor PU-H71 preferentially targets tumor-enriched Hsp90 complexes and affinity captures Hsp90-dependent oncogenic client proteins. We have used PU-H71 affinity capture to design a proteomic approach that, when combined with bioinformatic pathway analysis, identifies dysregulated signaling networks and key oncoproteins in chronic myeloid leukemia. The identified interactome overlaps with the well-characterized altered proteome in this cancer, indicating that this method can provide global insights into the biology of individual tumors, including primary patient specimens. In addition, we show that this approach can be used to identify previously uncharacterized oncoproteins and mechanisms, potentially leading to new targeted therapies. We further show that the abundance of the PU-H71-enriched Hsp90 species, which is not dictated by Hsp90 expression alone, is predictive of the cell's sensitivity to Hsp90 inhibition. © 2011 Nature America, Inc. All rights reserved. |
| Keywords: | signal transduction; controlled study; protein expression; unclassified drug; oncoprotein; human cell; antineoplastic agent; binding affinity; protein targeting; protein binding; genetic transcription; chronic myeloid leukemia; proteomics; molecular mechanics; cancer cell; heat shock protein 90; molecular interaction; ic 50; bioinformatics; stat5 protein; pu h 71 |
| Journal Title: | Nature Chemical Biology |
| Volume: | 7 |
| Issue: | 11 |
| ISSN: | 1552-4450 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2011-11-01 |
| Start Page: | 818 |
| End Page: | 826 |
| Language: | English |
| DOI: | 10.1038/nchembio.670 |
| PROVIDER: | scopus |
| PUBMED: | 21946277 |
| PMCID: | PMC3265389 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 9 December 2011" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work