14-3-3σ regulates B-cell homeostasis through stabilization of FOXO1

被引：36

作者：

Su, Yu-Wen ^{[1
,2
]}

Hao, Zhenyue ^{[1
]}

Hirao, Atsushi ^{[1
,3
]}

Yamamoto, Kazuo ^{[1
]}

Lin, Wen-Jye ^{[1
]}

Young, Ashley ^{[1
]}

Duncan, Gordon S. ^{[1
]}

Yoshida, Hiroki ^{[1
,4
]}

Wakeham, Andrew ^{[1
]}

Lang, Philipp A. ^{[1
]}

Murakami, Kiichi ^{[1
]}

Ohashi, Pamela ^{[1
]}

Mak, Tak W. ^{[1
]}

Hermeking, Heiko

Vogelstein, Bert

机构：

[1] Univ Hlth Network, Ontario Canc Inst, Campbell Family Canc Res Inst, Toronto, ON M5G 2C1, Canada

[2] Natl Hlth Res Inst, Dept Immunol Res Ctr, Zhunan 35053, Taiwan

[3] Kanazawa Univ, Canc Res Inst, Ctr Canc & Stem Cell Res, Div Mol Genet, Kanazawa, Ishikawa 9200934, Japan

[4] Saga Univ, Fac Med, Dept Biomol Sci, Saga 840, Japan

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 04期

关键词：

FORKHEAD TRANSCRIPTION FACTOR; VESICULAR STOMATITIS-VIRUS; GENE-EXPRESSION; MICE; PROTEINS; SURVIVAL; AKT; DIFFERENTIATION; IMMUNOGLOBULIN; SUPPRESSION;

D O I：

10.1073/pnas.1017729108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

14-3-3 sigma regulates cytokinesis and cell cycle arrest induced by DNA damage but its role in the immune system is unknown. Using gene-targeted 14-3-3 sigma-deficient (i.e., KO) mice, we studied the role of 14-3-3 sigma in B-cell functions. Total numbers of B cells were reduced by spontaneous apoptosis of peripheral B cells. Upon B-cell antigen receptor engagement in vitro, KO B cells did not proliferate properly or up-regulate CD86. In response to T cell-independent antigens, KO B cells showed poor secretion of antigen-specific IgM. This deficit led to increased lethality of KO mice after vesicular stomatitis virus infection. KO B cells showed elevated total FOXO transcriptional activity but also increased FOXO1 degradation. Coimmunoprecipitation revealed that endogenous 14-3-3 sigma protein formed a complex with FOXO1 protein. Our results suggest that 14-3-3 sigma maintains FOXO1 at a consistent level critical for normal B-cell antigen receptor signaling and B-cell survival.

引用

页码：1555 / 1560

页数：6

共 40 条

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