Prunustatin A, a novel GRP78 molecular chaperone down-regulator isolated from Streptomyces violaceoniger.
In the course of our screening program for regulators of a molecular chaperone GRP78 expression, we isolated a novel inhibitor of GRP78 expression, designated as prunustatin A, from Streptomyces violaceoniger 4521-SVS3. The structure of prunustatin A was determined by a series of NMR analyses to be an oxidized type of the neoantimycin family. Prunustatin A inhibited the expression of GRP78 induced by 2-deoxyglucose in human fibrosarcoma HT1080 cells accompanied by global cell death without showing cytotoxicity under normal nutrient condition.
Umeda
Yukiko
Y
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan.
Chijiwa
Shuhei
S
Furihata
Kazuo
K
Furihata
Keiko
K
Sakuda
Shohei
S
Nagasawa
Hiromichi
H
Watanabe
Hidenori
H
Shin-ya
Kazuo
K
D002460:Cell Line; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003847:Deoxyglucose / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D017930:Genes, Reporter; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics*; D006801:Humans; D008156:Luciferases / Q000235:genetics; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors* / Q000235:genetics*; D015394:Molecular Structure; D011401:Promoter Regions, Genetic; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013302:Streptomyces / Q000737:chemistry* / Q000302:isolation & purification
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018942:Macrolides; D018832:Molecular Chaperones; C501241:prunustatin A; D003847:Deoxyglucose; D008156:Luciferases