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
Journal ArticleDOI
High levels of heat shock protein Hsp72 in cancer cells suppress default senescence pathways.
TL;DR: Hsp72 provides a selective advantage to cancer cells by suppressing default senescence via p53-dependent and p53 -independent pathways.
Journal ArticleDOI
Death by chaperone: HSP90, HSP70 or both?
TL;DR: The possible implications of the research for the development of HSP70 family modulators which offer not only the possibility of inhibiting H SP70 activity but also the simultaneous inhibition of H SP90, resulting in extensive tumour-specific apoptosis are discussed.
Journal ArticleDOI
Protein levels of heat shock proteins 27, 32, 60, 70, 90 and thioredoxin-1 in amnestic mild cognitive impairment: an investigation on the role of cellular stress response in the progression of Alzheimer disease.
Fabio Di Domenico,Rukhsana Sultana,Georgianne F. Tiu,Nicole N. Scheff,Marzia Perluigi,Chiara Cini,D. Allan Butterfield +6 more
TL;DR: The results show a general induction of HSPs and decreased levels of Thioredoxin 1 in aMCI brain suggesting that alteration in the chaperone protein systems might contribute to the pathogenesis and progression of AD.
Book ChapterDOI
Hsp70: Anti-apoptotic and Tumorigenic Protein
TL;DR: Hsp70 tumorigenic functions as well as the strategies that are being developed in cancer therapy in order to inhibit Hsp70 are commented in this chapter.
Journal ArticleDOI
The role of oxidative DNA damage in radiation induced bystander effect
Sophia Havaki,Athanassios Kotsinas,Efstathios Chronopoulos,Dimitris Kletsas,Alexandros G. Georgakilas,Vassilis G. Gorgoulis,Vassilis G. Gorgoulis,Vassilis G. Gorgoulis +7 more
TL;DR: The role of oxidative stress in the induction of bystander effects is presented referring to the types of the implicated oxidative DNA lesions, the contributing intercellular and intracellular stress mediators, the way they are transmitted from irradiated to bystander cells and the complex role of the bystander effect in the therapeutic efficacy of radiation treatment of cancer.
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.