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

AUTOR(ES)

Shinyashiki, Masaru

FONTE

The National Academy of Sciences

RESUMO

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 O2-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.

Documentos Relacionados

• Cooperative activation of a eukaryotic transcription factor: interaction between Cu(I) and yeast ACE1 protein.
• Revisiting the kinetics of nitric oxide (NO) binding to soluble guanylate cyclase: The simple NO-binding model is incorrect
• The reduction potential of nitric oxide (NO) and its importance to NO biochemistry
• Tumor necrosis factor (TNF) and nitric oxide (NO) mediate the acute cardiovascular effects of endotoxemia.
• Interaction of yeast kinetochore proteins with centromere–protein/transcription factor Cbf1