Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion

Tiziana Bonaldi, Fabio Talamo, Paola Scaffidi, Denise Ferrera, Annalisa Porto, Angela Bachi, Anna Rubartelli, Alessandra Agresti, Marco E. Bianchi

Research output: Contribution to journalArticle

Abstract

High Mobility Group 1 protein (HMGB1) is a chromatin component that, when leaked out by necrotic cells, triggers inflammation. HMGB1 can also be secreted by activated monocytes and macrophages, and functions as a late mediator of inflammation. Secretion of a nuclear protein requires a tightly controlled relocation program. We show here that in all cells HMGB1 shuttles actively between the nucleus and cytoplasm. Monocytes and macrophages acetylate HMGB1 extensively upon activation with lipopolysaccharide; moreover, forced hyperacetylation of HMGB1 in resting macrophages causes its relocalization to the cytosol. Cytosolic HMGB1 is then concentrated by default into secretory lysosomes, and secreted when monocytic cells receive an appropriate second signal.

Original languageEnglish
Pages (from-to)5551-5560
Number of pages10
JournalEMBO Journal
Volume22
Issue number20
DOIs
Publication statusPublished - Oct 15 2003

Keywords

  • Histones
  • HMGB
  • Inflammation
  • NES
  • NLS
  • Sepsis

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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