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22 (20): 5551-5560

Copyright © 2003 by the European Molecular Biology Organization.

Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion

Tiziana Bonaldi1,2, Fabio Talamo1, Paola Scaffidi3, Denise Ferrera4, Annalisa Porto1,5, Angela Bachi1, Anna Rubartelli4, Alessandra Agresti1,6, and Marco E. Bianchi3,6

1 DIBIT, San Raffaele Scientific Institute, 3 San Raffaele University, via Olgettina 58, 20132 Milan, 4 National Cancer Research Institute, largo Rosanna Benzi 10, 16132 Genoa and 5 Institute of Cardiology, Catholic University, largo A. Gemelli 8, 00168 Rome, Italy 2 Present address: Adolf-Butenandt Institute, Department of Molecular Biology, Protein Analysis Unit, University of Munich, Schillerstrasse 44, D-80336 Munich, Germany 6 Corresponding authors e-mail: bianchi.marco{at}hsr.it and agresti.alessandra{at}hsr.it

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.

Key Words: Keywords: histones/HMGB/inflammation/NLS/NES/sepsis

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Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882