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A proteomic approach towards the Hsp90‐dependent ubiquitinylated proteome
Author(s) -
Falsone S. Fabio,
Gesslbauer Bernd,
Rek Angelika,
Kungl Andreas J.
Publication year - 2007
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200600996
Subject(s) - hsp90 , proteome , proteasome , signal transduction , transcription factor , biology , proteomics , transcription (linguistics) , ubiquitin , hela , gene , computational biology , biochemistry , microbiology and biotechnology , heat shock protein , cell , linguistics , philosophy
Since many Hsp90 client proteins are key players in tumour pathways, the ubiquitylation and subsequent degradation of Hsp90‐substrates as a consequence of pharmacologically inhibiting Hsp90 represents an innovative approach for cancer therapy. We therefore identified Hsp90‐binding proteins which accumulated as ubiquityl‐tagged aggregates in the detergent insoluble fraction of HeLa cells as a consequence of simultaneously inhibiting Hsp90 and the proteasome. 2‐DE followed by nanoLC‐MS/MS of trypsinised protein spots provided the Hsp90‐dependent ubiquitylated proteome which was finally annotated and functionally classified. The overall picture thus obtained emphasised the well‐established role of Hsp90 in stabilising proteins involved in gene transcription and signal transduction. It also provided a novel Hsp90‐related link to metabolic pathways as the inhibition of Hsp90 caused the ubiquitylation of a significant amount of metabolic enzymes. These findings serve to support cumulating indications which attribute Hsp90 to diverse stabilising functions beyond signal transduction and gene transcription.