Abstract
Proteasome assembling chaperone (PAC) 3 acts as a homodimer and plays an important role in proteasome formation. We screened JBIR-22 (1) as an inhibitor for protein-protein interaction (PPI) of PAC3 homodimer from our natural product library using a protein fragment complementation assay (PCA) with monomeric Kusabira-Green fluorescent protein (mKG) in vitro and found that 1 exhibited potent inhibitory activity against PAC3 homodimerization. Compound 1 showed long-term cytotoxicity against the human cervical carcinoma cell line, HeLa. This is the first report of a PPI inhibitor for proteasome assembly factors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Drug Screening Assays, Antitumor
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Female
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HeLa Cells
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Humans
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Molecular Structure
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Proteasome Endopeptidase Complex / drug effects*
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Proteasome Endopeptidase Complex / metabolism
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Proteins / analysis*
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Proteins / drug effects
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Proteins / metabolism
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Pyrrolidinones / chemical synthesis
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Pyrrolidinones / chemistry*
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Pyrrolidinones / pharmacology*
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Tetrahydronaphthalenes / chemical synthesis
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Tetrahydronaphthalenes / chemistry*
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Tetrahydronaphthalenes / pharmacology*
Substances
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JBIR-22
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Proteins
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Pyrrolidinones
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Tetrahydronaphthalenes
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equisetin
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Proteasome Endopeptidase Complex