Structural highlights
FunctionENPL_CANLF Molecular chaperone that functions in the processing and transport of secreted proteins. When associated with CNPY3, required for proper folding of Toll-like receptors. Functions in endoplasmic reticulum associated degradation (ERAD). Has ATPase activity (By similarity). Publication Abstract from PubMedThe heat shock protein 90 (Hsp90) family of molecular chaperones regulates protein homeostasis, folding, and degradation. The ER-resident Hsp90 isoform, glucose-regulated protein 94 (Grp94), promotes the aggregation of mutant forms of myocilin, a protein associated with primary open-angle glaucoma. While inhibition of Grp94 promotes the degradation of mutant myocilin in vitro, to date no Grp94-selective inhibitors have been investigated in vivo. Here, a Grp94-selective inhibitor facilitated mutant myocilin degradation and rescued phenotypes in a transgenic mouse model of hereditary primary open-angle glaucoma. Ocular toxicities previously associated with pan-Hsp90 inhibitors were not evident with our Grp94-selective inhibitor, 4-Br-BnIm. Our study suggests that selective inhibition of a distinct Hsp90 family member holds translational promise for ocular and other diseases associated with cell stress and protein misfolding. Isoform-selective Hsp90 inhibition rescues model of hereditary open-angle glaucoma.,Stothert AR, Suntharalingam A, Tang X, Crowley VM, Mishra SJ, Webster JM, Nordhues BA, Huard DJE, Passaglia CL, Lieberman RL, Blagg BSJ, Blair LJ, Koren J 3rd, Dickey CA Sci Rep. 2017 Dec 20;7(1):17951. doi: 10.1038/s41598-017-18344-4. PMID:29263415[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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