Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion.
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.
Bonaldi
Tiziana
T
DIBIT, San Raffaele Scientific Institute, San Raffaele University, via Olgettina 58, 20132 Milan, Italy.
Talamo
Fabio
F
Scaffidi
Paola
P
Ferrera
Denise
D
Porto
Annalisa
A
Bachi
Angela
A
Rubartelli
Anna
A
Agresti
Alessandra
A
Bianchi
Marco E
ME
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
D024243:HMGB1 Protein; D028884:Karyopherins; D010446:Peptide Fragments; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D000097606:Exportin 1 Protein