Search results for "Co-chaperone"
showing 4 items of 4 documents
Breaking BAG: The Co-Chaperone BAG3 in Health and Disease.
2016
Human BAG ( B cl-2-associated a thano g ene) proteins form a family of antiapoptotic proteins that currently consists of six members (BAG1–6) all sharing the BAG protein domain from which the name arises. Via this domain, BAG proteins bind to the heat shock protein 70 (Hsp70), thereby acting as a co-chaperone regulating the activity of Hsp70. In addition to their antiapoptotic activity, all human BAG proteins have distinct functions in health and disease, and BAG3 in particular is the focus of many investigations. BAG3 has a modular protein domain composition offering the possibility for manifold interactions with other proteins. Various BAG3 functions are implicated in disorders including …
The role of the co-chaperone BAG3 in selective macroautophagy: implications for aging and disease
2012
Maintenance of protein homeostasis, correct protein folding, refolding and clearance is of central importance for the function and survival of every cell. Here, the degradation of proteins is of particular importance, especially during aging and certain degenerative disorders when the protein load is increased. During cellular aging as well as under acute stress, there is a reciprocal change in expression of two members of the BAG (Bcl-2-associated athanogene) family, BAG1 and BAG3. While BAG1 serves an important function during the degradation of ubiquitinated proteins via the proteasome, BAG3 is the mediator of a novel macroautophagy pathway. This BAG3-mediated macroautophagy is based on …
Chaperonopathies of senescence and the scrambling of interactions between the chaperoning and the immune systems
2010
Aging entails progressive deterioration of molecules and supramolecular structures, including Hsp chaperones and their complexes, paralleled by functional decline. Recent research has changed our views on Hsp chaperones. They work inside and outside cells in many locations, alone or forming teams, interacting with cells, receptors, and molecules that are not chaperones, in roles that are not typically attributed to chaperones, such as protein folding. Hsp chaperones form a physiological system with a variety of functions and interactions with other systems, for example, the immune system. We propose that chaperone malfunctioning due to structural damage or gene dysregulation during aging ha…
Discovery and validation of small-molecule heat-shock protein 90 inhibitors through multimodality molecular imaging in living subjects.
2012
Up-regulation of the folding machinery of the heat-shock protein 90 (Hsp90) chaperone protein is crucial for cancer progression. The two Hsp90 isoforms (α and β) play different roles in response to chemotherapy. To identify isoform-selective inhibitors of Hsp90(α/β)/cochaperone p23 interactions, we developed a dual-luciferase (Renilla and Firefly) reporter system for high-throughput screening (HTS) and monitoring the efficacy of Hsp90 inhibitors in cell culture and live mice. HTS of a 30,176 small-molecule chemical library in cell culture identified a compound, N -(5-methylisoxazol-3-yl)-2-[4-(thiophen-2-yl)-6-(trifluoromethyl)pyrimidin-2-ylthio]acetamide (CP9), that binds to Hsp90(α/β) an…