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