Document Detail


14-3-3sigma regulates B-cell homeostasis through stabilization of FOXO1.
MedLine Citation:
PMID:  21205887     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
14-3-3σ regulates cytokinesis and cell cycle arrest induced by DNA damage but its role in the immune system is unknown. Using gene-targeted 14-3-3σ-deficient (i.e., KO) mice, we studied the role of 14-3-3σ 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 14-3-3σ protein formed a complex with FOXO1 protein. Our results suggest that 14-3-3σ maintains FOXO1 at a consistent level critical for normal B-cell antigen receptor signaling and B-cell survival.
Authors:
Yu-Wen Su; Zhenyue Hao; Atsushi Hirao; Kazuo Yamamoto; Wen-Jye Lin; Ashley Young; Gordon S Duncan; Hiroki Yoshida; Andrew Wakeham; Philipp A Lang; Kiichi Murakami; Heiko Hermeking; Bert Vogelstein; Pamela Ohashi; Tak W Mak
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-01-04
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-26     Completed Date:  2011-04-26     Revised Date:  2013-11-05    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1555-60     Citation Subset:  IM    
Affiliation:
Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada M5G 2C1.
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MeSH Terms
Descriptor/Qualifier:
14-3-3 Proteins / genetics,  immunology*,  metabolism
Adoptive Transfer
Animals
Antigens / immunology
Apoptosis / immunology
B-Lymphocytes / cytology,  immunology*,  metabolism
Blotting, Western
Cell Proliferation
Cells, Cultured
Enzyme-Linked Immunosorbent Assay
Female
Ficoll / analogs & derivatives,  immunology
Forkhead Transcription Factors / genetics,  immunology*,  metabolism
Homeostasis / immunology*
Immunoglobulin G / blood
Immunoglobulin M / blood
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Protein Binding
Receptors, Antigen, B-Cell / immunology
Reverse Transcriptase Polymerase Chain Reaction
Trinitrobenzenes / immunology
Chemical
Reg. No./Substance:
0/14-3-3 Proteins; 0/Antigens; 0/Forkhead Transcription Factors; 0/Foxo1 protein, mouse; 0/Immunoglobulin G; 0/Immunoglobulin M; 0/Receptors, Antigen, B-Cell; 0/Sfn protein, mouse; 0/TNP-ficoll; 0/Trinitrobenzenes; 25702-74-3/Ficoll
Comments/Corrections
Erratum In:
Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):15849
Proc Natl Acad Sci U S A. 2011 Apr 19;108(16):6689
Note: Hermeking, Heiko [added]; Vogelstein, Bert [added]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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