Interaction - Based High - Throughput Screen to Identify Inhibitors of Hsp 90 - CochaperoneTMAn
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منابع مشابه
A novel class of small molecule inhibitors of Hsp90.
Unregulated cellular proliferation, caused by mutation or dysregulation of growth-promoting proteins, is an underlying cause of cancer. Many such growth-promoting proteins exhibit an increased dependence on the activity of the chaperone heat-shock protein 90 (Hsp90) for correct folding and maturation in the cell. One can therefore envision that inhibition of Hsp90 would be an effective and broa...
متن کاملThe Interaction Network of the Hsp90 Molecular Chaperone
P. Wong · E. R. M. Tillier Department of Medical Biophysics , University of Toronto , Toronto , ON , Canada Abstract Heat shock protein 90 (Hsp 90) is a highly abundant and critical molecular chaperone that plays key roles in cellular quality control systems. The Hsp90 mechanism of function has been the subject of extensive investigation by many groups using traditional biochemical approaches a...
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The use of small molecule inhibitors of cellular processes is a powerful approach to understanding gene function that complements the genetic approach. We have designed a high throughput screen to identify new inhibitors of eukaryotic protein synthesis. We used a bicistronic mRNA reporter to multiplex our assay and simultaneously screen for inhibitors of cap-dependent initiation, internal initi...
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The human antigen R (HuR) stabilizes many mRNAs of proto-oncogene, transcription factors, cytokines and growth factors by recognizing AU-rich elements (AREs) presented in their 3' or 5' untranslated region (UTR). Multiple lines of experimental evidence suggest that this process plays a key role in cancer development. Thus, destabilizing HuR/RNA interaction by small molecules presents an opportu...
متن کاملTargeting heat shock response to sensitize cancer cells to proteasome and Hsp90 inhibitors.
Novel classes of anticancer drugs, including proteasome inhibitors and Hsp90 inhibitors, potently induce heat shock proteins (Hsps). Because Hsps show antiapoptotic activities, we suggested that suppression of such induction may sensitize cancer cells to these drugs. Here, we knocked out the major heat shock transcription factor HSF-1 in several cancer cell lines using small interfering RNA and...
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