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Published on: August 21, 2013
Targeting hsp90 family members: A strategy to improve cancer cell death
Pedro Buc Calderon1, Raphaël Beck2, Christophe Glorieux2
1Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Belgium; Facultad de Ciencias de la Salud, Universidad Arturo Prat, Iquique, Chile.
Abstract:
A crucial process in biology is the conversion of the genetic information into functional proteins that carry out the genetic program. However, a supplementary step is required to obtain functional proteins: the folding of the newly translated polypeptides into well-defined, three-dimensional conformations. Proteins chaperones are crucial for this final step in the readout of genetic information, which results in the formation of functional proteins. In this review, a special attention will be given to the strategies targeting hsp90 family members in order to increase cancer cell death. We argue that disruption of hsp90 machinery and the further client protein degradation is the main consequence of hsp90 oxidative cleavage taking place at the N-terminal nucleotide-binding site. Moreover, modulation of Grp94 expression will be discussed as a potential therapeutic goal looking for a decrease in cancer relapses.
Insights
Heat shock protein 90 (Hsp90) chaperones are vital for protein folding. Targeting Hsp90, particularly through oxidative cleavage, can disrupt cancer cell machinery, leading to protein degradation and potential therapeutic benefits.
Area of Science:
- Molecular Biology
- Biochemistry
- Cancer Research
Background:
- Protein folding is essential for cellular function, converting genetic information into functional proteins.
- Protein chaperones, like Hsp90, are critical for achieving correct three-dimensional protein conformations.
- Dysregulation of protein folding is implicated in various diseases, including cancer.
Purpose of the Study:
- To review strategies targeting Hsp90 family members for cancer therapy.
- To elucidate the consequences of Hsp90 disruption, specifically oxidative cleavage.
- To explore the therapeutic potential of modulating Grp94 expression in cancer.
Main Methods:
- Review of existing literature on Hsp90 function and targeting.
- Analysis of mechanisms involving Hsp90 oxidative cleavage at the N-terminal nucleotide-binding site.
- Discussion of Grp94 (an Hsp90 family member) expression modulation.
Main Results:
- Disruption of Hsp90 machinery leads to client protein degradation.
- Oxidative cleavage of Hsp90 at its N-terminal nucleotide-binding site is a key mechanism.
- Modulating Grp94 expression presents a potential strategy to reduce cancer recurrence.
Conclusions:
- Targeting Hsp90 offers a promising avenue for increasing cancer cell death.
- Understanding Hsp90's role in protein homeostasis is crucial for developing novel cancer therapies.
- Modulating Grp94 may be a valuable therapeutic goal to prevent cancer relapses.
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