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Article Dans Une Revue Journal of Biomolecular Screening Année : 2007

High-Content Classification of Nucleocytoplasmic Import or Export Inhibitors

Résumé

Transcription factors of the nuclear factor kappa B family are the paradigm for signaling dependent nuclear translocation and are ideally suited to analysis through image-based chemical genetic screening. The authors describe combining high-content image analysis with a compound screen to identify compounds affecting either nuclear import or export. Validation in silico and in vitro determined an EC(50) for the nuclear export blocker leptomycin B of 2.4 ng/mL (4.4 nM). The method demonstrated high selectivity (Z' >0.95), speed, and robustness in a screen of a compound collection. It identified the IkappaB protein kinase inhibitor BAY 11 7082 as an import inhibitor, the p38 mitogen-activated protein (MAP) kinase inhibitor PD98509 as an import enhancer, and phorbol ester as an export inhibitor. The results establish a robust method for identifying compounds regulating nucleocytoplasmic import or export and also implicate MAP kinases in nuclear import of nuclear factor kappa B.

Dates et versions

hal-02425950 , version 1 (15-08-2020)

Identifiants

Citer

Yong-Jun Kwon, Auguste Genovesio, Nam Youl Kim, Hi Chul Kim, Sungyong Jung, et al.. High-Content Classification of Nucleocytoplasmic Import or Export Inhibitors. Journal of Biomolecular Screening, 2007, 12 (5), pp.621-627. ⟨10.1177/1087057107301319⟩. ⟨hal-02425950⟩
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