Functional interaction of the immunosuppressant mizoribine with the 14-3-3 protein

Shu Takahashi; Hideki Wakui; Jan Åke Gustafsson; Johanna Zilliacus; Hideaki Itoh

doi:10.1006/bbrc.2000.3104

Functional interaction of the immunosuppressant mizoribine with the 14-3-3 protein

Shu Takahashi, Hideki Wakui, Jan Åke Gustafsson, Johanna Zilliacus, Hideaki Itoh

Research output: Contribution to journal › Article › peer-review

86 Scopus citations

Abstract

Mizoribine (MIZ) is a novel imidazole nucleoside with immunosuppressive activity. MIZ has been approved in Japan and combination therapy with MIZ and glucocorticoids has been used after renal transplantation and for lupus nephritis and rheumatoid arthritis. In this study, we identify 14-3-3 proteins as MIZ-binding proteins. 14-3-3 proteins interact with many proteins involved in cellular signaling, including the glucocorticoid receptor (GR). The 14-3-3/GR interaction enhances the transcriptional activity of the receptor. We show that MIZ affects the conformation of 14-3-3 proteins and enhances the interaction of GR and 14-3-3 η dose dependently in vitro. MIZ also has a stimulatory effect on transcriptional activation by the GR. Our results point to the possibility that one mechanism for the therapeutic effect of MIZ could be to regulate the GR function via 14-3-3 proteins. (C) 2000 Academic Press.

Original language	English (US)
Pages (from-to)	87-92
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	274
Issue number	1
DOIs	https://doi.org/10.1006/bbrc.2000.3104
State	Published - Jul 21 2000

Keywords

14-3-3
Glucocorticoid receptor
Immunosuppression
Mizoribine
Nuclear receptor
Transactivation

ASJC Scopus subject areas

Biochemistry
Biophysics
Molecular Biology

Access to Document

10.1006/bbrc.2000.3104

Cite this

@article{b18481d851e049bbb5ca11eb31d4f2be,

title = "Functional interaction of the immunosuppressant mizoribine with the 14-3-3 protein",

abstract = "Mizoribine (MIZ) is a novel imidazole nucleoside with immunosuppressive activity. MIZ has been approved in Japan and combination therapy with MIZ and glucocorticoids has been used after renal transplantation and for lupus nephritis and rheumatoid arthritis. In this study, we identify 14-3-3 proteins as MIZ-binding proteins. 14-3-3 proteins interact with many proteins involved in cellular signaling, including the glucocorticoid receptor (GR). The 14-3-3/GR interaction enhances the transcriptional activity of the receptor. We show that MIZ affects the conformation of 14-3-3 proteins and enhances the interaction of GR and 14-3-3 η dose dependently in vitro. MIZ also has a stimulatory effect on transcriptional activation by the GR. Our results point to the possibility that one mechanism for the therapeutic effect of MIZ could be to regulate the GR function via 14-3-3 proteins. (C) 2000 Academic Press.",

keywords = "14-3-3, Glucocorticoid receptor, Immunosuppression, Mizoribine, Nuclear receptor, Transactivation",

author = "Shu Takahashi and Hideki Wakui and Gustafsson, {Jan {\AA}ke} and Johanna Zilliacus and Hideaki Itoh",

note = "Funding Information: This work was supported by grants from the Swedish Medical Research Council (12557), {\AA}ke Wiberg Foundation, Lars Hierta Foundation, and Emil and Wera Cornell Foundation and in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (11671024). Johannna Zilliacus was supported by a junior research position from the Swedish Research Council.",

year = "2000",

month = jul,

day = "21",

doi = "10.1006/bbrc.2000.3104",

language = "English (US)",

volume = "274",

pages = "87--92",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Academic Press",

number = "1",

}

TY - JOUR

T1 - Functional interaction of the immunosuppressant mizoribine with the 14-3-3 protein

AU - Takahashi, Shu

AU - Wakui, Hideki

AU - Gustafsson, Jan Åke

AU - Zilliacus, Johanna

AU - Itoh, Hideaki

N1 - Funding Information: This work was supported by grants from the Swedish Medical Research Council (12557), Åke Wiberg Foundation, Lars Hierta Foundation, and Emil and Wera Cornell Foundation and in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (11671024). Johannna Zilliacus was supported by a junior research position from the Swedish Research Council.

PY - 2000/7/21

Y1 - 2000/7/21

N2 - Mizoribine (MIZ) is a novel imidazole nucleoside with immunosuppressive activity. MIZ has been approved in Japan and combination therapy with MIZ and glucocorticoids has been used after renal transplantation and for lupus nephritis and rheumatoid arthritis. In this study, we identify 14-3-3 proteins as MIZ-binding proteins. 14-3-3 proteins interact with many proteins involved in cellular signaling, including the glucocorticoid receptor (GR). The 14-3-3/GR interaction enhances the transcriptional activity of the receptor. We show that MIZ affects the conformation of 14-3-3 proteins and enhances the interaction of GR and 14-3-3 η dose dependently in vitro. MIZ also has a stimulatory effect on transcriptional activation by the GR. Our results point to the possibility that one mechanism for the therapeutic effect of MIZ could be to regulate the GR function via 14-3-3 proteins. (C) 2000 Academic Press.

AB - Mizoribine (MIZ) is a novel imidazole nucleoside with immunosuppressive activity. MIZ has been approved in Japan and combination therapy with MIZ and glucocorticoids has been used after renal transplantation and for lupus nephritis and rheumatoid arthritis. In this study, we identify 14-3-3 proteins as MIZ-binding proteins. 14-3-3 proteins interact with many proteins involved in cellular signaling, including the glucocorticoid receptor (GR). The 14-3-3/GR interaction enhances the transcriptional activity of the receptor. We show that MIZ affects the conformation of 14-3-3 proteins and enhances the interaction of GR and 14-3-3 η dose dependently in vitro. MIZ also has a stimulatory effect on transcriptional activation by the GR. Our results point to the possibility that one mechanism for the therapeutic effect of MIZ could be to regulate the GR function via 14-3-3 proteins. (C) 2000 Academic Press.

KW - 14-3-3

KW - Glucocorticoid receptor

KW - Immunosuppression

KW - Mizoribine

KW - Nuclear receptor

KW - Transactivation

UR - http://www.scopus.com/inward/record.url?scp=0033930704&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033930704&partnerID=8YFLogxK

U2 - 10.1006/bbrc.2000.3104

DO - 10.1006/bbrc.2000.3104

M3 - Article

C2 - 10903900

AN - SCOPUS:0033930704

SN - 0006-291X

VL - 274

SP - 87

EP - 92

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 1

ER -

Functional interaction of the immunosuppressant mizoribine with the 14-3-3 protein

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this