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.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Shinyashiki, M; Chiang, KT; Switzer, CH; Gralla, EB; Valentine, JS; Thiele, DJ; Fukuto, JM

Published Date

  • March 14, 2000

Published In

Volume / Issue

  • 97 / 6

Start / End Page

  • 2491 - 2496

PubMed ID

  • 10694579

Pubmed Central ID

  • 10694579

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.050586597


  • eng

Conference Location

  • United States