Dear Editor:Geldanamycin is a benzoquinone ansamycin,which wasoriginally described as a tyrosine kinase inhibitor.How-ever,subsequent studies have revealed that geldanamycinbinds to and inhibits heat-shock protein 90(...Dear Editor:Geldanamycin is a benzoquinone ansamycin,which wasoriginally described as a tyrosine kinase inhibitor.How-ever,subsequent studies have revealed that geldanamycinbinds to and inhibits heat-shock protein 90(Hsp90)activity[1].Hsp90 is a molecular chaperone involved in the con-formational maturation of proteins such as mutated p53,Raf-1,Akt,Bcr-Ab1,and ErbB2.It is suggested that agentsinhibiting Hsp90 have anti-cancer properties,although theprecise molecular mechanisms underlying the anti-cancereffects of geldanamycin are not well understood.Increasing evidence has suggested that diabetes andneurodegenerative disorders such as Parkinson's andAlzheimer's diseases are related to the disruption ofendoplasmic reticulum(ER)function.In response to ERstress,unfolded proteins accumulate and aggregate in theER,which will trigger many rescuer responses,includingthe unfolded protein response(UPR)and ER-associateddegradation.Interestingly,geldanamycin has been shownto upregulate ER chaperones and the expression of CHOP[2].Moreover,Hsp90 associates with PERK and IRE1α,ER-resident trans-membrane protein kinases involved inER stress response[3].These observations suggest展开更多
文摘Dear Editor:Geldanamycin is a benzoquinone ansamycin,which wasoriginally described as a tyrosine kinase inhibitor.How-ever,subsequent studies have revealed that geldanamycinbinds to and inhibits heat-shock protein 90(Hsp90)activity[1].Hsp90 is a molecular chaperone involved in the con-formational maturation of proteins such as mutated p53,Raf-1,Akt,Bcr-Ab1,and ErbB2.It is suggested that agentsinhibiting Hsp90 have anti-cancer properties,although theprecise molecular mechanisms underlying the anti-cancereffects of geldanamycin are not well understood.Increasing evidence has suggested that diabetes andneurodegenerative disorders such as Parkinson's andAlzheimer's diseases are related to the disruption ofendoplasmic reticulum(ER)function.In response to ERstress,unfolded proteins accumulate and aggregate in theER,which will trigger many rescuer responses,includingthe unfolded protein response(UPR)and ER-associateddegradation.Interestingly,geldanamycin has been shownto upregulate ER chaperones and the expression of CHOP[2].Moreover,Hsp90 associates with PERK and IRE1α,ER-resident trans-membrane protein kinases involved inER stress response[3].These observations suggest
