Oxidation of zinc finger transcription factors: Physiological consequences

K. A. Webster, H. Prentice, N. H. Bishopric

Research output: Contribution to journalReview articlepeer-review

109 Scopus citations

Abstract

Redox-sensitive cysteine residues are present in the interaction domains of many protein complexes. There are examples in all of the major categories of transcription factors, including basic region, leucine zipper, helix-loop-helix, and zinc finger. Zinc finger structures require at least two zinc-coordinated cysteine sulfhydryl groups, and oxidation or alkylation of these can eliminate DNA-binding and transcriptional functions. We review here the evidence for oxidation of zinc finger cysteines, the pathways and reactive oxygen intermediates involved, and the functional and physiological consequences of these reactions. Despite skepticism that the strongly reducing intracellular environment would permit significant oxidation of cysteine residues within zinc finger transcription factors, there is compelling evidence that oxidation occurs both in vitro and in vivo. Early reports demonstrating reversible oxidation of zinc-coordinated cysteines with loss of binding function in vitro were shown to reflect accurately the changes in intact cells, and these in turn have been shown to correlate with physiological changes. In particular, the accumulation of oxidized Sp1 zinc fingers during aging, and estrogen receptors in tamoxifen-resistant breast cancers are dramatic examples of what may be a general sensitivity of zinc finger factors to changes in the redox state of the cell.

Original languageEnglish (US)
Pages (from-to)535-548
Number of pages14
JournalAntioxidants and Redox Signaling
Volume3
Issue number4
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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