Document Detail


Critical role of Pcid2 in B cell survival through the regulation of MAD2 expression.
MedLine Citation:
PMID:  20870947     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mitotic checkpoint is essential for maintaining genomic stability in differentiating B cells undergoing genetic alterations of the Ig gene. In this study, using real-time RT-PCR and in situ RNA hybridization, we demonstrated that MAD2 mRNA export is selectively regulated by Pcid2/Thp1. Pcid2 small interfering RNA induced a cell-cycle abnormality with increased apoptosis and polyploidy, as previously observed in MAD2-knockdown cells. Pcid2 small interfering RNA reduced MAD2 expression, but not the expression of other cell-cycle checkpoint proteins, such as MAD1 and BUBR1, or the cell-cycle-associated proteins, cyclin A, cyclin B1, and cyclin-dependent kinase 1. In mouse B lineage cells, Pcid2 transcripts appeared in a stage-dependent manner at high levels in bone marrow pre-B and immature B cells, and in spleen transitional 1 and follicular B cells, but at lower levels in pro-B, transitional 2, and marginal zone B cells, suggesting a stage-dependent requirement for MAD2 regulation. Cd19-cre-derived targeting of the Pcid2 gene induced a mature B cell deficiency in mice. These findings indicate that Pcid2 is essential for B cell survival through the regulation of MAD2 expression during B cell differentiation.
Authors:
Teruo Nakaya; Kazuhiko Kuwahara; Kazutaka Ohta; Masahiro Kitabatake; Teppei Toda; Naoki Takeda; Tokio Tani; Eisaku Kondo; Nobuo Sakaguchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-24
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  185     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-21     Completed Date:  2010-11-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5180-7     Citation Subset:  AIM; IM    
Affiliation:
Department of Immunology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
B-Lymphocytes / cytology*,  immunology,  metabolism
Cell Cycle / genetics,  immunology
Cell Cycle Proteins / biosynthesis,  genetics,  immunology,  metabolism*
Cell Differentiation / immunology
Cell Survival / genetics,  immunology
Gene Expression
Gene Expression Regulation / immunology*
Immunoblotting
Immunohistochemistry
In Situ Hybridization
Mice
Mice, Knockout
RNA, Small Interfering
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/MAD2 protein, mouse; 0/RNA, Small Interfering

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