Identification and validation of calmodulin as a binding protein of an anti-proliferative small molecule 3,4-dihydroisoquinolinium salt

Hye Jin Jung, Joong Sup Shim, Jungchan Park, Hyun Joon Ha, Jung Ho Kim, Joong Gon Kim, Nam Doo Kim, Jeong Hyeok Yoon, Ho Jeong Kwon

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

IHY-153 (2-(2,5-difluorobenzyl)-3,4-dihydro-5-(10-hydroxydecyl)-6- methoxy-1-undecylisoquinolinium bromide) was recently discovered as a small molecule that potently inhibits proliferation of tumor cells by inducing cell-cycle arrest at G0-G1 phase. To investigate the basis of anti-proliferative activity of IHY-153, cellular binding proteins of biotinyl-IHY-153 were screened using T7 phage displayed human cDNA libraries. Calmodulin-expressing phage specifically bound to immobilized IHY-153 in a Ca2+-dependent manner. The interaction between IHY-153 and Ca2+//CaM was validated through phage competition binding assays, surface plasmon resonance analysis, and molecular modeling. IHY-153 induced sustained phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and subsequently increased p21WAF1 expression in colon cancer cells. These results demonstrate that IHY-153, a novel small molecule, targets Ca2+/CaM and indicate that this compound functions as an anti-proliferative agent by influencing Ca2+/CaM- dependent signal transduction.

Original languageEnglish
Pages (from-to)423-432
Number of pages10
JournalProteomics - Clinical Applications
Volume3
Issue number4
DOIs
Publication statusPublished - 2009 May 14

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Bacteriophages
Calmodulin
Carrier Proteins
Salts
Cells
Bacteriophage T7
Cell Cycle Resting Phase
Molecules
Mitogen-Activated Protein Kinase 3
Surface Plasmon Resonance
Mitogen-Activated Protein Kinase 1
G1 Phase
Cell Cycle Checkpoints
Bromides
Gene Library
Colonic Neoplasms
Signal Transduction
Signal transduction
Phosphorylation
Molecular modeling

All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry

Cite this

Jung, Hye Jin ; Shim, Joong Sup ; Park, Jungchan ; Ha, Hyun Joon ; Kim, Jung Ho ; Kim, Joong Gon ; Kim, Nam Doo ; Yoon, Jeong Hyeok ; Kwon, Ho Jeong. / Identification and validation of calmodulin as a binding protein of an anti-proliferative small molecule 3,4-dihydroisoquinolinium salt. In: Proteomics - Clinical Applications. 2009 ; Vol. 3, No. 4. pp. 423-432.
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Identification and validation of calmodulin as a binding protein of an anti-proliferative small molecule 3,4-dihydroisoquinolinium salt. / Jung, Hye Jin; Shim, Joong Sup; Park, Jungchan; Ha, Hyun Joon; Kim, Jung Ho; Kim, Joong Gon; Kim, Nam Doo; Yoon, Jeong Hyeok; Kwon, Ho Jeong.

In: Proteomics - Clinical Applications, Vol. 3, No. 4, 14.05.2009, p. 423-432.

Research output: Contribution to journalArticle

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AU - Kim, Jung Ho

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AU - Yoon, Jeong Hyeok

AU - Kwon, Ho Jeong

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