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Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion.
- Source :
-
The EMBO journal [EMBO J] 2003 Oct 15; Vol. 22 (20), pp. 5551-60. - Publication Year :
- 2003
-
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.
- Subjects :
- Acetylation
Amino Acid Sequence
Animals
Base Sequence
Cells, Cultured
Electrophoresis, Gel, Two-Dimensional
HMGB1 Protein chemistry
HMGB1 Protein genetics
HMGB1 Protein isolation & purification
HeLa Cells
Humans
Karyopherins genetics
Karyopherins metabolism
Mice
Molecular Sequence Data
Peptide Fragments chemistry
Protein Biosynthesis
Recombinant Fusion Proteins metabolism
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Transcription, Genetic
Exportin 1 Protein
HMGB1 Protein physiology
Inflammation physiopathology
Monocytes physiology
Receptors, Cytoplasmic and Nuclear
Subjects
Details
- Language :
- English
- ISSN :
- 0261-4189
- Volume :
- 22
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 14532127
- Full Text :
- https://doi.org/10.1093/emboj/cdg516