Abstract
Geldanamycin (GA), herbimycin A and radicicol bind heat-shock protein-90 (Hsp90) and destabilize its client proteins including v-Src, Bcr-Abl, Raf-1, ErbB2, some growth factor receptors and steroid receptors. Thus, Hsp90-active agents induce ubiquitination and proteasomal degradation of numerous oncoproteins. Depending on the cellular context, HSP90-active agents cause growth arrest, differentiation and apoptosis, or can prevent apoptosis. HSP-active agents are undergoing clinical trials. Like targets of most chemotherapeutics, Hsp90 is not a cancer-specific protein. By attacking a nonspecific target, HSP-90-active compounds still may preferentially kill certain tumor cells. How can this be achieved? How can therapeutic potentials be exploited? This article starts the discussion.
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Blagosklonny, M. Hsp-90-associated oncoproteins: multiple targets of geldanamycin and its analogs. Leukemia 16, 455–462 (2002). https://doi.org/10.1038/sj.leu.2402415
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