Identification of poly(rC) binding protein 2 (PCBP2) as a target protein of immunosuppressive agent 15-deoxyspergualin

Masataka Murahashi, Siro Simizu, Masahiko Morioka, Kazuo Umezawa

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

15-Deoxyspergualin (DSG) is an immunosuppressive agent being clinically used. Unlike tacrolimus and cyclosporine A, it does not inhibit the calcineurin pathway, and its mechanism of action and target molecule have not been elucidated. Therefore, we previously prepared biotinylated derivative of DSG (BDSG) to fish up the target protein. In the present research, we identified poly(rC) binding protein 2 (PCBP2) as a DSG-binding protein using this probe. DSG was confirmed to bind to PCBP2 by pull-down assay. Intracellular localization of PCBP2 was changed from the nucleus to the cytoplasm by DSG treatment. DSG inhibited the cell growth, and over-expression of PCBP2 reduced the anti-proliferative activity of DSG. PCBP2 is known to regulate various proteins including STAT1/2. Thus, we found PCBP2 as the first target protein of DSG that can explain the immunosuppressive activity.

Original languageEnglish
JournalBiochemical and Biophysical Research Communications
DOIs
Publication statusAccepted/In press - 2016 May 19

Fingerprint

Immunosuppressive Agents
Carrier Proteins
Proteins
STAT1 Transcription Factor
gusperimus
Calcineurin
Cell growth
Tacrolimus
Fish
Cyclosporine
Assays
Cytoplasm
Fishes
Derivatives
Molecules
Growth
Research

Keywords

  • 15-Deoxyspergualin
  • Biotin conjugate
  • Poly(rC) binding protein 2 (PCBP2)
  • Signal transducer and activator of transcription (STAT)
  • Target protein

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Identification of poly(rC) binding protein 2 (PCBP2) as a target protein of immunosuppressive agent 15-deoxyspergualin. / Murahashi, Masataka; Simizu, Siro; Morioka, Masahiko; Umezawa, Kazuo.

In: Biochemical and Biophysical Research Communications, 19.05.2016.

Research output: Contribution to journalArticle

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AU - Morioka, Masahiko

AU - Umezawa, Kazuo

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AB - 15-Deoxyspergualin (DSG) is an immunosuppressive agent being clinically used. Unlike tacrolimus and cyclosporine A, it does not inhibit the calcineurin pathway, and its mechanism of action and target molecule have not been elucidated. Therefore, we previously prepared biotinylated derivative of DSG (BDSG) to fish up the target protein. In the present research, we identified poly(rC) binding protein 2 (PCBP2) as a DSG-binding protein using this probe. DSG was confirmed to bind to PCBP2 by pull-down assay. Intracellular localization of PCBP2 was changed from the nucleus to the cytoplasm by DSG treatment. DSG inhibited the cell growth, and over-expression of PCBP2 reduced the anti-proliferative activity of DSG. PCBP2 is known to regulate various proteins including STAT1/2. Thus, we found PCBP2 as the first target protein of DSG that can explain the immunosuppressive activity.

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