Identification of a new target molecule for a cascade therapy of polycystic kidney.
Autosomal dominant polycystic kidney disease is a systemic disorder that primary affects the kidney which is characterized by the formation of fluid-filled cysts in both kidneys that leads to progressive renal failure. Mutated genes, polycystin-1 and polycystin-2, are identified, and evidence has emerged that polycystins are ion channels or regulators of ion channels. In spite of extensive characterization of polycystins, how polycystin channel signaling may be involved in cyst formation in ADPKD is still unclear. We found a mutant mouse which exhibits polycystic kidney and bone deformity in the course of making a transgenic mouse carrying the Drosophila sex-lethal gene. We identified a mutated gene Makorin1 by positional cloning. Makorin1 carries a typical RING-finger motif, suggesting that Makorin1 belongs to ubiquitinase E3 family. Makorin1 would open a new avenue to understand pathogenesis of polycystic kidney, and become a new therapeutic target of polycystic kidney.
Yoshida
Noriyuki
N
Division of Chemical Biology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Yano
Yoshihisa
Y
Yoshiki
Atsushi
A
Ueno
Munehisa
M
Deguchi
Nobuhiro
N
Hirotsune
Shinji
S
D000818:Animals; D015316:Genetic Therapy / Q000379:methods* / Q000639:trends; D006801:Humans; D007473:Ion Channels / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D016254:Mutagenesis, Insertional; D009154:Mutation; D009419:Nerve Tissue Proteins; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012261:Ribonucleoproteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D050396:TRPP Cation Channels
D007473:Ion Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D012261:Ribonucleoproteins; D050396:TRPP Cation Channels; C410808:Makorin ring finger protein 1