TY - JOUR
T1 - Identification of poly(rC) binding protein 2 (PCBP2) as a target protein of immunosuppressive agent 15-deoxyspergualin
AU - Murahashi, Masataka
AU - Simizu, Siro
AU - Morioka, Masahiko
AU - Umezawa, Kazuo
N1 - Funding Information:
This work was supported by the Application Research of Changzhou Science and Technique Bureau ( CJ20130028 ).
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/8/5
Y1 - 2016/8/5
N2 - 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.
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.
KW - 15-Deoxyspergualin
KW - Biotin conjugate
KW - Poly(rC) binding protein 2 (PCBP2)
KW - Signal transducer and activator of transcription (STAT)
KW - Target protein
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U2 - 10.1016/j.bbrc.2016.05.142
DO - 10.1016/j.bbrc.2016.05.142
M3 - Article
C2 - 27261432
AN - SCOPUS:84973558710
SN - 0006-291X
VL - 476
SP - 445
EP - 449
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -