Document Detail


Ran overexpression leads to diminished T cell responses and selectively modulates nuclear levels of c-Jun and c-Fos.
MedLine Citation:
PMID:  20028981     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ras-related nuclear protein (Ran) is a Ras family GTPase, and its documented functions are the regulation of DNA replication, cell cycle progression, nuclear structure formation, RNA processing and exportation, and nuclear protein importation. In this study, we performed detailed mapping of Ran expression during mouse ontogeny using in situ hybridization. High Ran expression was found in various organs and tissues including the thymus cortex and spleen white pulp. Ran was induced in T cells 24 h after their activation. The function of Ran in the immune system was investigated using Ran transgenic (Tg) mice. In Ran Tg T cells, there was compromised activation marker expression, lymphokine secretion, and proliferation upon T cell receptor activation in vitro when compared with wild type T cells. Tg mice also manifested defective delayed type hypersensitivity in vivo. Upon PMA and ionomycin stimulation, Tg T cells were defective in nuclear accumulation of AP-1 factors (c-Jun and c-Fos) but not NF-kappaB family members. Our experiments showed that Ran had important regulatory function in T cell activation. One of the possible mechanisms is that intracellular Ran protein levels control the nuclear retention for selective transcription factors such as c-Jun and c-Fos of AP-1, which is known to be critical in T cell activation and proliferation and lymphokine secretion.
Authors:
Xiaoying Qiao; Diep Ngoc Thi Pham; Hongyu Luo; Jiangping Wu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-22
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-15     Completed Date:  2010-03-11     Revised Date:  2011-07-25    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5488-96     Citation Subset:  IM    
Affiliation:
Laboratory of Immunology, Centre de Recherche, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec H2L 4M1, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Proliferation / drug effects
Cytokines / biosynthesis,  genetics,  immunology
Genes, fos / immunology*
Genes, jun / immunology*
Hypersensitivity, Delayed / genetics,  immunology,  metabolism
Lymphocyte Activation / drug effects,  immunology*
Mice
Mice, Transgenic
Receptors, Antigen, T-Cell / genetics,  immunology
T-Lymphocytes / immunology*,  metabolism
Transcription Factor AP-1 / genetics,  immunology*,  metabolism
ran GTP-Binding Protein / genetics,  immunology*,  metabolism
Grant Support
ID/Acronym/Agency:
IMH-79565//Canadian Institutes of Health Research; MOP57697//Canadian Institutes of Health Research; MOP69089//Canadian Institutes of Health Research; MOP97829//Canadian Institutes of Health Research; PPP86159//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Cytokines; 0/Ran protein, mouse; 0/Receptors, Antigen, T-Cell; 0/Transcription Factor AP-1; EC 3.6.5.2/ran GTP-Binding Protein
Comments/Corrections

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