JBIR-22, an inhibitor for protein-protein interaction of the homodimer of proteasome assembly factor 3

Miho Izumikawa; Junko Hashimoto; Takatsugu Hirokawa; Satoshi Sugimoto; Taira Kato; Motoki Takagi; Kazuo Shin-Ya

doi:10.1021/np900788e

JBIR-22, an inhibitor for protein-protein interaction of the homodimer of proteasome assembly factor 3

J Nat Prod. 2010 Apr 23;73(4):628-31. doi: 10.1021/np900788e.

Authors

Miho Izumikawa¹, Junko Hashimoto, Takatsugu Hirokawa, Satoshi Sugimoto, Taira Kato, Motoki Takagi, Kazuo Shin-Ya

Affiliation

¹ Biomedicinal Information Research Center (BIRC), Japan Biological Informatics Consortium (JBIC), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan.

PMID: 20180542
DOI: 10.1021/np900788e

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

Research Support, Non-U.S. Gov't

MeSH terms

Drug Screening Assays, Antitumor
Female
HeLa Cells
Humans
Molecular Structure
Proteasome Endopeptidase Complex / drug effects*
Proteasome Endopeptidase Complex / metabolism
Proteins / analysis*
Proteins / drug effects
Proteins / metabolism
Pyrrolidinones / chemical synthesis
Pyrrolidinones / chemistry*
Pyrrolidinones / pharmacology*
Tetrahydronaphthalenes / chemical synthesis
Tetrahydronaphthalenes / chemistry*
Tetrahydronaphthalenes / pharmacology*

Substances

JBIR-22
Proteins
Pyrrolidinones
Tetrahydronaphthalenes
equisetin
Proteasome Endopeptidase Complex