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Fluorescent biosensors for the detection of HMGB1 release.

Martins, I; Kepp, O; Menger, L; Michaud, M; Adjemian, S; Sukkurwala, AQ; Vacchelli, E; ... Kroemer, G; + view all (2013) Fluorescent biosensors for the detection of HMGB1 release. Methods Mol Biol , 1004 pp. 43-56. 10.1007/978-1-62703-383-1_4.

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Abstract

During necrosis and following some instances of apoptosis (in particular in the absence of a proficient phagocytic system), the nonhistone chromatin component high-mobility group box 1 (HMGB1) is released in the extracellular space. In vivo, extracellular HMGB1 can bind Toll-like receptor 4 on the surface of dendritic cells, de facto operating as a danger-associated molecular pattern and alarming the organism to the presence of stressful conditions. Recent results indicate that the release of HMGB1 is one of the key features for cell death to be perceived as immunogenic, i.e., to be capable of triggering a cognate immune response in vivo. Thus, only anticancer agents that-among other features-allow for the release of HMGB1 as they induce cell death are expected to stimulate anticancer immune responses. To investigate the immunogenic potential of conventional anticancer agents and novel cell death inducers on a high-throughput scale, we engineered human osteosarcoma U2OS cells to express HMGB1 fused at the N-terminus of the green fluorescent protein (GFP). Coupled to fluorescence microscopy workstations for automated image acquisition and analysis, this HMGB1-GFP-based biosensor is amenable for the identification of potential inducers of immunogenic cell death among large chemical libraries.

Type: Article
Title: Fluorescent biosensors for the detection of HMGB1 release.
Location: United States
DOI: 10.1007/978-1-62703-383-1_4
Keywords: Biosensing Techniques, Cell Death, Cells, Cultured, Green Fluorescent Proteins, HMGB1 Protein, Humans, Image Processing, Computer-Assisted, Microscopy, Fluorescence, Recombinant Fusion Proteins
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/1411110
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