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Tuesday 20 April 2004

hsp90, hsp-90


Definition: Heat shock protein 90 (Hsp90) is a molecular chaperone whose association is required for the stability and function of multiple mutated, chimeric and over-expressed signaling proteins that promote the growth and/or survival of cancer cells.

Hsp90 is a key regulator of approximately 100 ’client’ proteins crucial for numerous cell signaling processes. Hsp90 client proteins include mutated p53, Bcr-Abl, Raf-1, Akt, ErbB2 and hypoxia-inducible factor 1 alpha (HIF-1 alpha).

The heat shock protein 90 (HSP90) chaperone machinery is a key regulator of proteostasis under both physiological and stress conditions in eukaryotic cells.

As HSP90 has several hundred protein substrates (or ’clients’), it is involved in many cellular processes beyond protein folding, which include DNA repair, development, the immune response and neurodegenerative disease.

large number of co-chaperones interact with HSP90 and regulate the ATPase-associated conformational changes of the HSP90 dimer that occur during the processing of clients.

Owing to the importance of HSP90 in the regulation of many cellular proteins, it has become a promising drug target for the treatment of several diseases, which include cancer and diseases associated with protein misfolding.

Targeted therapy

- hsp90 inhibitors

Payall References

- The HSP90 chaperone machinery. Schopf FH, Biebl MM, Buchner J.
Nat Rev Mol Cell Biol. 2017 Apr 21. doi : 10.1038/nrm.2017.20
PMID: 28429788

- Chaperone protein gets personal. Nature, 2017. doi : 10.1038/nature22487. http://go.nature com/2pYRLFO

- Whitesell L, Lindquist SL. HSP90 and the chaperoning of cancer. Nat Rev Cancer. 2005 Oct;5(10):761-72. PMID: 16175177

- Aoyagi S, Archer TK. Modulating molecular chaperone Hsp90 functions through reversible acetylation. Trends Cell Biol. 2005 Nov;15(11):565-7. PMID: 16199163

- Matthews RC, Burnie JP. Human recombinant antibody to HSP90: a natural partner in combination therapy. Curr Mol Med. 2005 Jun;5(4):403-11. PMID: 15977996

- Ruden DM, Xiao L, Garfinkel MD, Lu X. Hsp90 and environmental impacts on epigenetic states: a model for the trans-generational effects of diethylstibesterol on uterine development and cancer. Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R149-55. PMID: 15809267

- Pearl LH. Hsp90 and Cdc37 — a chaperone cancer conspiracy. Curr Opin Genet Dev. 2005 Feb;15(1):55-61. PMID: 15661534

- Kamal A, Boehm MF, Burrows FJ. Therapeutic and diagnostic implications of Hsp90 activation. Trends Mol Med. 2004 Jun;10(6):283-90. PMID: 15177193

- Workman P. Altered states: selectively drugging the Hsp90 cancer chaperone. Trends Mol Med. 2004 Feb;10(2):47-51. PMID: 15106614

- Neckers L. Hsp90 inhibitors as novel cancer chemotherapeutic agents. Trends Mol Med. 2002;8(4 Suppl):S55-61. PMID: 11927289