Molecular chaperones and the stress of oncogenesis.
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TLDR
It has been established that heat-shock proteins exhibit specificity to particular classes of polypeptide substrates and client proteins in vivo, and that chaperones can stabilize mutations that affect the folded conformation.Abstract:
Protein-damaging stresses induce the expression of 'heat-shock proteins', which have essential roles in protecting cells from the potentially lethal effects of stress and proteotoxicity. These stress-protective heat-shock proteins are often overexpressed in cells of various cancers and have been suggested to be contributing factors in tumorigenesis. An underlying basis of oncogenesis is the acquisition and accumulation of mutations that provide the transformed cell with the combined characteristics of deregulated cell proliferation and suppressed cell death. Heat-shock proteins with dual roles as regulators of protein conformation and stress sensors may therefore have intriguing and central roles in both cell proliferation and apoptosis. It has been established that heat-shock proteins exhibit specificity to particular classes of polypeptide substrates and client proteins in vivo, and that chaperones can stabilize mutations that affect the folded conformation. Likewise, overexpression of chaperones has also been shown to protect cells against apoptotic cell death. The involvement of chaperones, therefore, in such diverse roles might suggest novel anticancer therapeutic approaches targeting heat-shock protein function for a broad spectrum of tumor types.read more
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Journal ArticleDOI
The carboxyl-terminal domain of inducible Hsp70 protects from ischemic injury in vivo and in vitro
Yunjuan Sun,Yi Bing Ouyang,Lijun Xu,Ari Man Yi Chow,Robin L. Anderson,James G. Hecker,Rona G. Giffard +6 more
TL;DR: The results show that the carboxyl-terminal portion of Hsp70 is sufficient for neuroprotection, indicating that neither the ability to fold denatured proteins nor interactions with cochaperones or other proteins that bind the amino- terminal half of HSP70 are essential to ischemic protection.
Journal ArticleDOI
Heat shock factor 1 ameliorates proteotoxicity in cooperation with the transcription factor NFAT.
Naoki Hayashida,Mitsuaki Fujimoto,Ke Tan,Ramachandran Prakasam,Toyohide Shinkawa,Liangping Li,Hitoshi Ichikawa,Ryosuke Takii,Akira Nakai +8 more
TL;DR: These results show the first mechanistic basis for the observation that HSF1 has a much more profound effect on proteostasis than individual Hsp or combination of different Hsps, and suggest a new pathway for ameliorating protein‐misfolding diseases.
Book ChapterDOI
Hsp70 chaperone as a survival factor in cell pathology.
TL;DR: Hsp70 was shown to be expressed on the surface of cancer cells and to participate in the presentation of tumor antigens to immune cells, and the chaperone activity of Hsp70 is an important factor that should be taken into consideration in cancer therapy.
Journal ArticleDOI
Protective Effect of Carnosine During Nitrosative Stress in Astroglial Cell Cultures
Vittorio Calabrese,C Colombrita,E Guagliano,Maria Sapienza,A. Ravagna,Venera Cardile,Giovanni Scapagnini,Anna Maria Santoro,Andrea Mangiameli,David Allan Butterfield,A. M. Giuffrida Stella,Enrico Rizzarelli +11 more
TL;DR: Carnosine protected against nitric oxide-induced impairment of mitochondrial function and was associated with decreased formation of oxidatively modified proteins and with decreased up-regulation oxidative stress-responsive genes, such as Hsp32, Hsp70 and mt-SOD.
Journal ArticleDOI
17β-Estradiol, Aging, Inflammation, and the Stress Response in the Female Heart
James P. Stice,Le Chen,Se-Chan Kim,J. S. Jung,A. L. Tran,Tingting Liu,Anne A Knowlton,Anne A Knowlton +7 more
TL;DR: It is demonstrated that while aging in female rats led to a loss of the cardioprotective HSP response, E(2) retains its protective cellular properties.
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