Disruption of the Raf-1-Hsp90 molecular complex results in destabilization of Raf-1 and loss of Raf-1-Ras association
- PMID: 7592678
- DOI: 10.1074/jbc.270.41.24585
Disruption of the Raf-1-Hsp90 molecular complex results in destabilization of Raf-1 and loss of Raf-1-Ras association
Abstract
Cytosolic Raf-1 exists in a high molecular weight complex with the heat shock protein Hsp90, the purpose of which is unknown. The benzoquinone ansamycin, geldanamycin, specifically binds to Hsp90 and disrupts certain multimolecular complexes containing this protein. Using this drug, we are able to demonstrate rapid dissociation of both Raf-1-Hsp90 and Raf-1-Ras multimolecular complexes, concomitant with a markedly decreased half-life of the Raf-1 protein. Continued disruption of the Raf-1-Hsp90 complex results in apparent loss of Raf-1 protein from the cell, although Raf-1 synthesis is actually increased. Prevention of Raf-1-Hsp90 complex formation interferes with trafficking of newly synthesized Raf-1 from cytosol to plasma membrane. These data indicate that association with Hsp90 is essential for both Raf-1 protein stability and its proper localization in the cell.
Similar articles
-
The hsp90-binding antibiotic geldanamycin decreases Raf levels and epidermal growth factor signaling without disrupting formation of signaling complexes or reducing the specific enzymatic activity of Raf kinase.J Biol Chem. 1997 Feb 14;272(7):4013-20. doi: 10.1074/jbc.272.7.4013. J Biol Chem. 1997. PMID: 9020108
-
Destabilization of Raf-1 by geldanamycin leads to disruption of the Raf-1-MEK-mitogen-activated protein kinase signalling pathway.Mol Cell Biol. 1996 Oct;16(10):5839-45. doi: 10.1128/MCB.16.10.5839. Mol Cell Biol. 1996. PMID: 8816498 Free PMC article.
-
The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin.Cancer Chemother Pharmacol. 1998;42(4):273-9. doi: 10.1007/s002800050817. Cancer Chemother Pharmacol. 1998. PMID: 9744771
-
Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity.Invest New Drugs. 1999;17(4):361-73. doi: 10.1023/a:1006382320697. Invest New Drugs. 1999. PMID: 10759403 Review.
-
Geldanamycin: the prototype of a class of antitumor drugs targeting the heat shock protein 90 family of molecular chaperones.Cell Stress Chaperones. 2001 Apr;6(2):105-12. doi: 10.1379/1466-1268(2001)006<0105:gtpoac>2.0.co;2. Cell Stress Chaperones. 2001. PMID: 11599571 Free PMC article. Review. No abstract available.
Cited by
-
Glioma: what is the role of c-Myc, hsp90 and telomerase?Mol Cell Biochem. 2006 Feb;283(1-2):1-9. doi: 10.1007/s11010-006-2495-z. Mol Cell Biochem. 2006. PMID: 16444580 Review.
-
Role of the heat shock protein 90 in immune response stimulation by bacterial DNA and synthetic oligonucleotides.Infect Immun. 2001 Sep;69(9):5546-52. doi: 10.1128/IAI.69.9.5546-5552.2001. Infect Immun. 2001. PMID: 11500428 Free PMC article.
-
Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26S proteasome.Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1032-7. doi: 10.1073/pnas.97.3.1032. Proc Natl Acad Sci U S A. 2000. PMID: 10655479 Free PMC article.
-
Interaction of Hsp90 with ribosomal proteins protects from ubiquitination and proteasome-dependent degradation.Mol Biol Cell. 2006 Feb;17(2):824-33. doi: 10.1091/mbc.e05-08-0713. Epub 2005 Nov 28. Mol Biol Cell. 2006. PMID: 16314389 Free PMC article.
-
Upregulation of ABCG2 by romidepsin via the aryl hydrocarbon receptor pathway.Mol Cancer Res. 2011 Apr;9(4):516-27. doi: 10.1158/1541-7786.MCR-10-0270. Epub 2011 Feb 25. Mol Cancer Res. 2011. PMID: 21357443 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous
