Hsp-90-associated oncoproteins: multiple targets of geldanamycin and its analogs.

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.

• Authors: M V Blagosklonny
• Journal: Leukemia (Leukemia) Vol. 16 Issue 4 Pg. 455-62 (Apr 2002) ISSN: 0887-6924 [Print] England
• PMID: 11960322 (Publication Type: Journal Article, Review)

Chemical References

• Antibiotics, Antineoplastic
• Benzoquinones
• Growth Inhibitors
• HSP90 Heat-Shock Proteins
• Lactams, Macrocyclic
• Oncogene Proteins
• Quinones
• Receptors, Growth Factor
• Transcription Factors
• Protein Kinases
• geldanamycin

Topics

• Animals
• Antibiotics, Antineoplastic (pharmacology)
• Benzoquinones
• Clinical Trials as Topic
• Growth Inhibitors (pharmacology)
• HSP90 Heat-Shock Proteins (antagonists & inhibitors)
• Humans
• Lactams, Macrocyclic
• Neoplasms (drug therapy, metabolism, pathology)
• Oncogene Proteins (metabolism)
• Protein Kinases (metabolism)
• Quinones (pharmacology)
• Receptors, Growth Factor (metabolism)
• Signal Transduction
• Transcription Factors (metabolism)