Molecular chaperones and the stress of oncogenesis.
Reads0
Chats0
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
Citations
More filters
Dissertation
Inhibición de hsp90 como nueva estrategia antitumoral contra el cáncer de páncreas exocrino y el cáncer de colon y recto
TL;DR: The use of the proteina de choque termico 90 (HSP90) as an antineoplasico unico and prometedor for the treatment of cancer colorrectal has been investigated in this paper.
Journal ArticleDOI
Genes Involved in the Cell Death Induced by Knockdown of Heat Shock Transcription Factor 1 in Human Oral Squamous Cell Carcinoma HSC-3 Cells
Hsp90-Mediated Maturation of Kinases andNuclear Steroid Hormone Receptors:A Dissertation
TL;DR: It is found that ATP binding and hydrolysis by Hsp90 are both required for the efficient maturation of the glucocorticoid hormone receptor (GR) and vsrc confirming the critical role of ATPHydrolysis in the m maturity of steroid hormone receptors and kinases in vivo.
Dissertation
Regulation of heat-induced cell death by the pro-apoptotic Bcl-2 family protein PUMA
TL;DR: Examination of the effect of hyperthermia on the BH3-only protein PUMA found that although protein levels were rapidly depleted following exposure to heat shock, levels of PUMA mRNA increased, which suggests that post-transcriptional mechanisms control the translation of PUma mRNA in heat-shocked cells.
References
More filters
Journal ArticleDOI
Mitogen-Activated Protein Kinase Pathways Mediated by ERK, JNK, and p38 Protein Kinases
Gary L. Johnson,Razvan Lapadat +1 more
TL;DR: Multicellular organisms have three well-characterized subfamilies of mitogen-activated protein kinases (MAPKs) that control a vast array of physiological processes, and inhibitors of these enzymes are being explored as anticancer agents.
Journal ArticleDOI
Molecular Chaperones in the Cytosol: from Nascent Chain to Folded Protein
TL;DR: Understanding how the thousands of different proteins synthesized in a cell use this chaperone machinery has profound implications for biotechnology and medicine.
Journal ArticleDOI
Hsp90 as a capacitor for morphological evolution
TL;DR: It is reported that when Drosophila Hsp90 is mutant or pharmacologically impaired, phenotypic variation affecting nearly any adult structure is produced, with specific variants depending on the genetic background and occurring both in laboratory strains and in wild populations.
Journal ArticleDOI
Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis.
Marcel Verheij,Marcel Verheij,Ron Bose,Xin Hua Lin,Bei Yao,W. David Jarvis,Steven Grant,Michael J. Birrer,Eva Szabo,Leonard I. Zon,John M. Kyriakis,Adriana Haimovitz-Friedman,Zvi Fuks,Richard Kolesnick +13 more
TL;DR: It is reported that ceramide initiates apoptosis through the SAPK cascade and evidence is provided for a signalling mechanism that integrates cytokine- and stress-activated apoptosis.
Journal ArticleDOI
Requirement of JNK for Stress- Induced Activation of the Cytochrome c-Mediated Death Pathway
Cathy Tournier,Patricia M. Hess,Derek D. Yang,Jie Xu,Tod K. Turner,Anjaruwee S. Nimnual,Dafna Bar-Sagi,Stephen N. Jones,Richard A. Flavell,Roger J. Davis +9 more
TL;DR: It is shown here that JNK is required for UV-induced apoptosis in primary murine embryonic fibroblasts, and data indicate that mitochondria are influenced by proapoptotic signal transduction through the JNK pathway.