Shock the heat shock network
Çiǧdem Atay, … , Serkan Uǧurlu, Nesrin Özören
Çiǧdem Atay, … , Serkan Uǧurlu, Nesrin Özören
Published February 23, 2009
Citation Information: J Clin Invest. 2009;119(3):445-447. https://doi.org/10.1172/JCI38681.
View: Text | PDF
Commentary

Shock the heat shock network

Abstract

The targeting of tumors is made possible through establishing protein signatures specific for each cancer type. The recent recognition of the higher expression levels of HSP90 and its accumulation in tumor cell mitochondria has made the HSP90 network a feasible target for neutralization. HSP90 antagonizes the mitochondrial permeability transition, blocking cytochrome c release and apoptosis. In this issue of the JCI, Kang et al. report the synthesis of Gamitrinibs, which target mitochondrially localized HSP90, specifically killing human cancer cell lines, and provide a fresh approach for cancer treatment (see the related article beginning on page 454).

Authors

Çiǧdem Atay, Serkan Uǧurlu, Nesrin Özören

×

Figure 1

Gamitrinibs target mitochondrially localized HSP90 in tumor cells and cause apoptosis.

Options: View larger image (or click on image) Download as PowerPoint
Gamitrinibs target mitochondrially localized HSP90 in tumor cells and ca...
In normal cells, mitochondrial outer membrane permeability is under the control of antiapoptotic (BCL2, BCLW, BCLXL) and proapoptotic (BAX/BAK) BCL2 family members and the permeability transition pore (PTP), which may include several components, such as the voltage-dependent anion channel, the adenine nucleotide translocator, and CYPD (13). HSP90 specifically accumulates in tumor cell mitochondria and inhibits the opening of the permeability transition pore by binding to CYPD, thus blocking both cytochrome c release and apoptosis. In the study by Kang et al. in this issue of the JCI (13), the addition of the mitochondrially targeted HSP90 blockers, the Gamitrinibs, results in the opening of the permeability transition pore and cytochrome c release, leading to tumor cell death.