Dynamic impacts of the inhibition of the molecular chaperone Hsp90 on the T-cell proteome have implications for anti-cancer therapy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:24312219", "kind": "science-record", "revision": 7, "content_hash": "sha256:8effca99a5c764f796c0bbfd74a48d573e5028c70b31192beef4cd5c35715f70", "created_at": "2026-11-01T15:40:04Z", "updated_at": "2026-11-01T21:58:15Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Dynamic impacts of the inhibition of the molecular chaperone Hsp90 on the T-cell proteome have implications for anti-cancer therapy.", "doi": "10.1371/journal.pone.0080425", "pmid": "24312219", "authors": ["Ivo Fierro-Monti", "Pablo Echeverria", "Julien Racle", "Celine Hernandez", "Didier Picard", "Manfredo Quadroni"], "journal": "PloS one", "year": 2013, "abstract": "The molecular chaperone Hsp90-dependent proteome represents a complex protein network of critical biological and medical relevance. Known to associate with proteins with a broad variety of functions termed clients, Hsp90 maintains key essential and oncogenic signalling pathways. Consequently, Hsp90 inhibitors are being tested as anti-cancer drugs. Using an integrated systematic approach to analyse the effects of Hsp90 inhibition in T-cells, we quantified differential changes in the Hsp90-dependent proteome, Hsp90 interactome, and a selection of the transcriptome. Kinetic behaviours in the Hsp90-dependent proteome were assessed using a novel pulse-chase strategy (Fierro-Monti et al., accompanying article), detecting effects on both protein stability and synthesis. Global and specific dynamic impacts, including proteostatic responses, are due to direct inhibition of Hsp90 as well as indirect effects. As a result, a decrease was detected in most proteins that changed their levels, including known Hsp90 clients. Most likely, consequences of the role of Hsp90 in gene expression determined a global reduction in net de novo protein synthesis. This decrease appeared to be greater in magnitude than a concomitantly observed global increase in protein decay rates. Several novel putative Hsp90 clients were validated, and interestingly, protein families with critical functions, particularly the Hsp90 family and cofactors themselves as well as protein kinases, displayed strongly increased decay rates due to Hsp90 inhibitor treatment. Remarkably, an upsurge in survival pathways, involving molecular chaperones and several oncoproteins, and decreased levels of some tumour suppressors, have implications for anti-cancer therapy with Hsp90 inhibitors. The diversity of global effects may represent a paradigm of mechanisms that are operating to shield cells from proteotoxic stress, by promoting pro-survival and anti-proliferative functions. 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A) Staining of li"], "order_basis": "paper_text_order:3306", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["lls in S phase. We assessed the induction of apoptosis by immunoblotting, detecting cleavage of the", "(PARP1), but observed no strong induction of apoptosis under the assay conditions (Fig. S1C). The d", "ntary Materials Figure S1 Cell viability and apoptosis of Jurkat cells treated for 24h with 1 µM ge", "by immunoblotting, detecting cleavage of the caspase substrate poly (ADP-ribose) polymerase (PARP"], "order_basis": "paper_text_order:3494", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["anamycin (GA) assessed by flow cytometry and western blot analysis. A) Staining of live cells with 7-a", "ic cells was visible (n = 2). C) Anti-PARP-1 western blot analysis. PARP-1 (110 kDa) is cleaved by Cas", "e. We assessed the induction of apoptosis by immunoblotting, detecting cleavage of the caspase substrate"], "order_basis": "paper_text_order:3507", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["axis) was compared with the one obtained for HeLa cells (1), with the one obtained for erythro", "e one obtained for erythroleukemia cell line K562, for the breast cancer line MD-MBA231, and f"], "order_basis": "paper_text_order:13755", "id": "assay:4"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["welch_t"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["For each time point, log2 of quantified ratios were subjected to a two-tailed Welch t-test for one sample (null hypothesis H0: µ = 0) followed by correction for multiple testing (Benjamini-Hochberg). 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