Impact of Posttranslational Modifications on the Anticancer Activity of Hsp90 Inhibitors.

摘要: Abstract Molecular chaperones are essential for guarding proteins that indispensable normal cellular functions. Heat shock protein 90 (Hsp90) is a vital molecular chaperone in eukaryotes participates stabilizing and activating approximately 200 target proteins, called “clients,” many of which involved signal transduction pathways. Cancer cells however utilize Hsp90 to an array mutated overexpressed oncoproteins protect them from misfolding degradation. Therefore, attractive cancer therapy. function relies on ATP binding hydrolysis, turn guides its carefully orchestrated conformational changes. This cycle fine-tuned by another group co-chaperones. They able accelerate or decelerate the cycle, allowing different clients. Posttranslational modifications (PTMs) can also regulate at epigenetic level thereby tailoring suit specific cell type environmental condition. Recent evidence suggests inhibition enzymes catalyze PTM act synergistically with inhibitors, providing novel therapeutic strategy enhance efficacy inhibitors cells.