A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors

By A. Kamal, Lia Thao, J. Sensintaffar, Lin Zhang, M. Boehm, L. Fritz, F. Burrows. Nature, 2003

1,419 citations recorded by the source corpus.

Subfields: Immunology, Materials Chemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/cb888b8e91561c511f429356116df681906b4192

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In Immunology

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In Materials Chemistry

In Molecular Biology

Citations in the corpus

HSP90 and the chaperoning of cancer (2005, background): “By contrast, in normal cells, there is a substantial pool of free HSP90 dimers that have low ATPase activity and low drug affinit”
SMYD2-dependent HSP90 methylation promotes cancer cell proliferation by regulating the chaperone complex formation. (2014, background): “A large amount of HSP90 complexes are present in cancer cells than in normal cells [48] and this cancer-specific chaperone machinery is likely to protect oncoproteins in cancer cells from misfolding and proteasomal degradation [1].”
Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks (2004, background): “The affinity of 17-AAG for HSP90 derived from tumor cells is 100-fold higher than for HSP90 from normal cells, which may explain the selectivity of HSP90 inhibitors for cancers (Kamal et al., 2003).”
Pathways of chaperone-mediated protein folding in the cytosol (2004, background): “Interestingly, the basic set of components that are involved in animal steroid-receptor maturation — HSP90, HSC70, HOP, HDJ1 and p23 — seem to be sufficient to form activated HSP90 complexes in vitro”
Functional proteomic screens reveal an essential extracellular role for hsp90α in cancer cell invasiveness (2004, background): “Recent studies show that hsp90 from tumour cells binds ATP with high affinity (39 ± 14 nM) in comparison with normal cell”
Systematic Mutant Analyses Elucidate General and Client-Specific Aspects of Hsp90 Function. (2016, background): “These partial inhibition strategies are sufficient to selectively inhibit many oncogenic clients, though the detailed mechanism for this selectivity is unclear (Kamal et al., 2003).”
Hsp90 molecular chaperone inhibitors: Are we there yet? (2012, background): “Hsp90 itself is often overexpressed (4) and present in an activated multichaperone complex in cancer cells (5), and it is now regarded as essential for malignant transformation and progression (2, 3).”
The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. (2007, background): “This observation is similar to that found in mutation-linked solid tumors (15, 17), which largely served as the basis for the introduction of Hsp90 inhibitors at the clinical level as an anticancer therapeutic.”
HSP90 at the hub of protein homeostasis: emerging mechanistic insights (2010, background): “In 2003, a high profile paper reported that many cancer cells have increased levels of co-chaperone-bound HSP90 (Ref”
Targeting the dynamic HSP90 complex in cancer (2010, background): “, and the sensitivity of HSP90 to inhibitors seems to be fundamentally different in tumour cells compared with normal cell”
When mutants gain new powers: news from the mutant p53 field (2009, neutral): “Because HSP90 is frequently over-activated in tumour”