| 14-3-3sigma regulates B-cell homeostasis through stabilization of FOXO1. | |
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MedLine Citation:
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PMID: 21205887 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-01-04 |
Journal Detail:
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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:
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Created Date: 2011-01-26 Completed Date: 2011-04-26 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 1555-60 Citation Subset: IM |
Affiliation:
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Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada M5G 2C1. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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14-3-3 Proteins
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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:
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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:
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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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