The interaction of nitric oxide (NO) with the yeast transcription factor Ace1: A model system for NO-protein thiol interactions with implications to metal metabolism.
Nitric oxide (NO) was found to inhibit the copper-dependent induction of the yeast CUP1 gene. This effect is attributable to an inhibition of the copper-responsive CUP1 transcriptional activator Ace1. A mechanism is proposed whereby the metal binding thiols of Ace1 are chemically modified via NO- and O(2)-dependent chemistry, thereby diminishing the ability of Ace1 to bind and respond to copper. Moreover, it is proposed that demetallated Ace1 is proteolytically degraded in the cell, resulting in a prolonged inhibition of copper-dependent CUP1 induction. These findings indicate that NO may serve as a disrupter of yeast copper metabolism. More importantly, considering the similarity of Ace1 to other mammalian metal-binding proteins, this work lends support to the hypothesis that NO may regulate/disrupt metal homeostasis under both normal physiological and pathophysiological circumstances.
Shinyashiki
M
M
Department of Pharmacology, University of California at Los Angeles Medical School, Center for the Health Sciences, Los Angeles, CA 90095-1735, USA.
Chiang
K T
KT
Switzer
C H
CH
Gralla
E B
EB
Valentine
J S
JS
Thiele
D J
DJ
Fukuto
J M
JM
D002352:Carrier Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005656:Fungal Proteins / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism; D008670:Metals / Q000378:metabolism*; D008956:Models, Chemical; D009569:Nitric Oxide / Q000378:metabolism*; D010957:Plasmids; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
C500769:CUP1-1 protein, S cerevisiae; C060256:CUP2 protein, S cerevisiae; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D008670:Metals; D000644:Quaternary Ammonium Compounds; D029701:Saccharomyces cerevisiae Proteins; D013438:Sulfhydryl Compounds; D014157:Transcription Factors; C007121:copper thionein; C406802:diethylammonium-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate; D009569:Nitric Oxide; D008668:Metallothionein; D001616:beta-Galactosidase