title: Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion.
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.
authors.affiliation: DIBIT, San Raffaele Scientific Institute, San Raffaele University, via Olgettina 58, 20132 Milan, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bonaldi
authors.forename: Fabio
authors.initials: F
authors.lastname: Talamo
authors.forename: Paola
authors.initials: P
authors.lastname: Scaffidi
authors.forename: Denise
authors.initials: D
authors.lastname: Ferrera
authors.forename: Annalisa
authors.initials: A
authors.lastname: Porto
authors.forename: Angela
authors.initials: A
authors.lastname: Bachi
authors.forename: Anna
authors.initials: A
authors.lastname: Rubartelli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Agresti
authors.forename: Marco E
authors.initials: ME
authors.lastname: Bianchi
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D015180:Electrophoresis, Gel, Two-Dimensional; D024243:HMGB1 Protein / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry; D014176:Protein Biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014158:Transcription, Genetic; D000097606:Exportin 1 Protein
chemical_list: D024243:HMGB1 Protein; D028884:Karyopherins; D010446:Peptide Fragments; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D000097606:Exportin 1 Protein