منابع مشابه
Functional Rescue of Trafficking-Impaired ABCB4 Mutants by Chemical Chaperones
Multidrug resistance protein 3 (MDR3, ABCB4) is a hepatocellular membrane protein that mediates biliary secretion of phosphatidylcholine. Null mutations in ABCB4 gene give rise to severe early-onset cholestatic liver disease. We have previously shown that the disease-associated mutations p.G68R, p.G228R, p.D459H, and p.A934T resulted in retention of ABCB4 in the endoplasmic reticulum, thus fail...
متن کاملRescue of atypical protein kinase C in epithelia by the cytoskeleton and Hsp70 family chaperones.
Atypical PKC (PKC iota) is a key organizer of cellular asymmetry. Sequential extractions of intestinal cells showed a pool of enzymatically active PKC iota and the chaperone Hsp70.1 attached to the apical cytoskeleton. Pull-down experiments using purified and recombinant proteins showed a complex of Hsp70 and atypical PKC on filamentous keratins. Transgenic animals overexpressing keratin 8 disp...
متن کاملRescue of vasopressin V2 receptor mutants by chemical chaperones: specificity and mechanism.
Because missense mutations in genetic diseases of membrane proteins often result in endoplasmic reticulum (ER) retention of functional proteins, drug-induced rescue of their cell surface expression and understanding the underlying mechanism are of clinical value. To study this, we tested chemical chaperones and sarco(endo)plasmic reticulum Ca2+ ATPase pump inhibitors on Madin-Darby canine kidne...
متن کاملFunctional Rescue of a Misfolded Drosophila melanogaster Dopamine Transporter Mutant Associated with a Sleepless Phenotype by Pharmacological Chaperones*♦
Folding-defective mutants of the human dopamine transporter (DAT) cause a syndrome of infantile dystonia/parkinsonism. Here, we provide a proof-of-principle that the folding deficit is amenable to correction in vivo by two means, the cognate DAT ligand noribogaine and the HSP70 inhibitor, pifithrin-μ. We examined the Drosophila melanogaster (d) mutant dDAT-G108Q, which leads to a sleepless phen...
متن کاملPharmacological Chaperones by Design
One of the most successful approaches in the synthesis of inhibitors of t he g lycosidases i s t he s ubstitution of t he e ndocyclic ox ygen i n monosaccharides by a nitrogen atom to get iminosugars. Given that many diseases h ave t heir o rigin i n t he malfunctioning of t hese e nzymes, t his glycomimetics bear s trong p otential a s dr ug c andidates. A t th eir p rotonated state, iminosuga...
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ژورنال
عنوان ژورنال: Nature Chemical Biology
سال: 2016
ISSN: 1552-4450,1552-4469
DOI: 10.1038/nchembio.2006