Alternative Approaches to Hsp90 Modulation for the Treatment of Cancer
Year: 2014
Type: article
Abstract: Hsp90 is responsible for the conformational maturation of newly synthesized polypeptides (client proteins) and the re-maturation of denatured proteins via the Hsp90 chaperone cycle. Inhibition of the Hsp90 N-terminus has emerged as a clinically relevant strategy for anticancer chemotherapeutics due to the involvement of clients in a variety of oncogenic pathways. Several immunophilins, co-chaperones and partner proteins are also necessary for Hsp90 chaperoning activity. Alternative strategies to inhibit Hsp90 function include disruption of the C-terminal dimerization domain and the Hsp90 heteroprotein complex. C-terminal inhibitors and Hsp90 co-chaperone disruptors prevent cancer cell proliferation similar to N-terminal inhibitors and destabilize client proteins without induction of heat shock proteins. Herein, current Hsp90 inhibitors, the chaperone cycle, and regulation of this cycle will be discussed.
Source: Future Medicinal Chemistry
DOI: 10.4155/fmc.14.89
Authors: Jessica A Hall, Leah K Forsberg, Brian Sj Blagg
Institution: University of Kansas
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: National Cancer Institute
OpenAlex ID: W2069185856