Molecular basis for the redox control of nuclear transport of the structural chromatin protein Hmgb1

George Hoppe, Katherine E. Talcott, Sanjoy K. Bhattacharya, John W. Crabb, Jonathan E. Sears

Research output: Contribution to journalArticlepeer-review

130 Scopus citations


Oxidative stress can induce a covalent disulfide bond between protein and peptide thiols that is reversible through enzymatic catalysis. This process provides a post-translational mechanism for control of protein function and may also protect thiol groups from irreversible oxidation. High mobility group protein B1 (Hmgb1), a DNA-binding structural chromosomal protein and transcriptional co-activator was identified as a substrate of glutaredoxin. Hmgb1 contains 3 cysteines, Cys23, 45, and 106. In mild oxidative conditions, Cys23 and Cys45 readily form an intramolecular disulfide bridge, whereas Cys106 remains in the reduced form. The disulfide bond between Cys23 and Cys45 is a target of glutathione-dependent reduction by glutaredoxin. Endogenous Hmgb1 as well as GFP-tagged wild-type Hmgb1 co-localize in the nucleus of CHO cells. While replacement of Hmgb1 Cys23 and/or 45 with serines did not affect the nuclear distribution of the mutant proteins, Cys106-to-Ser and triple cysteine mutations impaired nuclear localization of Hmgb1. Our cysteine targeted mutational analysis suggests that Cys23 and 45 induce conformational changes in response to oxidative stress, whereas Cys106 appears to be critical for the nucleocytoplasmic shuttling of Hmgb1.

Original languageEnglish (US)
Pages (from-to)3526-3538
Number of pages13
JournalExperimental Cell Research
Issue number18
StatePublished - Nov 1 2006
Externally publishedYes


  • Chromatin remodeling
  • Cysteine
  • GFP
  • Glutaredoxin
  • High mobility group
  • Oxidative stress
  • Thiol-disulfide reactions

ASJC Scopus subject areas

  • Cell Biology


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