Increased expression with differential subcellular location of cytidine deaminase APOBEC3G in human CD4+ T‐cell activation and dendritic cell maturation

APOBEC3G (apolipoprotein B mRNA editing enzyme catalytic polypeptide‐like 3G; A3G) is an innate defense protein showing activity against retroviruses and retrotransposons. Activated CD4+ T cells are highly permissive for HIV‐1 replication, whereas resting CD4+ T cells are refractory. Dendritic cells...

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Veröffentlicht in:Immunology and cell biology 2016-08, Vol.94 (7), p.689-700
Hauptverfasser: Oliva, Harold, Pacheco, Rodrigo, Martinez‐Navio, José M, Rodríguez‐García, Marta, Naranjo‐Gómez, Mar, Climent, Núria, Prado, Carolina, Gil, Cristina, Plana, Montserrat, García, Felipe, Miró, José M, Franco, Rafael, Borras, Francesc E, Navaratnam, Naveenan, Gatell, José M, Gallart, Teresa
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container_end_page 700
container_issue 7
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container_title Immunology and cell biology
container_volume 94
creator Oliva, Harold
Pacheco, Rodrigo
Martinez‐Navio, José M
Rodríguez‐García, Marta
Naranjo‐Gómez, Mar
Climent, Núria
Prado, Carolina
Gil, Cristina
Plana, Montserrat
García, Felipe
Miró, José M
Franco, Rafael
Borras, Francesc E
Navaratnam, Naveenan
Gatell, José M
Gallart, Teresa
description APOBEC3G (apolipoprotein B mRNA editing enzyme catalytic polypeptide‐like 3G; A3G) is an innate defense protein showing activity against retroviruses and retrotransposons. Activated CD4+ T cells are highly permissive for HIV‐1 replication, whereas resting CD4+ T cells are refractory. Dendritic cells (DCs), especially mature DCs, are also refractory. We investigated whether these differences could be related to a differential A3G expression and/or subcellular distribution. We found that A3G mRNA and protein expression is very low in resting CD4+ T cells and immature DCs, but increases strongly following T‐cell activation and DC maturation. The Apo‐7 anti‐A3G monoclonal antibody (mAb), which was specifically developed, confirmed these differences at the protein level and disclosed that A3G is mainly cytoplasmic in resting CD4+ T cells and immature DCs. Nevertheless, A3G translocates to the nucleus in activated‐proliferating CD4+ T cells, yet remaining cytoplasmic in matured DCs, a finding confirmed by immunoblotting analysis of cytoplasmic and nuclear fractions. Apo‐7 mAb was able to immunoprecipitate endogenous A3G allowing to detect complexes with numerous proteins in activated‐proliferating but not in resting CD4+ T cells. The results show for the first time the nuclear translocation of A3G in activated‐proliferating CD4+ T cells.
doi_str_mv 10.1038/icb.2016.28
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Apo‐7 mAb was able to immunoprecipitate endogenous A3G allowing to detect complexes with numerous proteins in activated‐proliferating but not in resting CD4+ T cells. 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Apo‐7 mAb was able to immunoprecipitate endogenous A3G allowing to detect complexes with numerous proteins in activated‐proliferating but not in resting CD4+ T cells. 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A3G) is an innate defense protein showing activity against retroviruses and retrotransposons. Activated CD4+ T cells are highly permissive for HIV‐1 replication, whereas resting CD4+ T cells are refractory. Dendritic cells (DCs), especially mature DCs, are also refractory. We investigated whether these differences could be related to a differential A3G expression and/or subcellular distribution. We found that A3G mRNA and protein expression is very low in resting CD4+ T cells and immature DCs, but increases strongly following T‐cell activation and DC maturation. The Apo‐7 anti‐A3G monoclonal antibody (mAb), which was specifically developed, confirmed these differences at the protein level and disclosed that A3G is mainly cytoplasmic in resting CD4+ T cells and immature DCs. Nevertheless, A3G translocates to the nucleus in activated‐proliferating CD4+ T cells, yet remaining cytoplasmic in matured DCs, a finding confirmed by immunoblotting analysis of cytoplasmic and nuclear fractions. Apo‐7 mAb was able to immunoprecipitate endogenous A3G allowing to detect complexes with numerous proteins in activated‐proliferating but not in resting CD4+ T cells. The results show for the first time the nuclear translocation of A3G in activated‐proliferating CD4+ T cells.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>26987686</pmid><doi>10.1038/icb.2016.28</doi><tpages>12</tpages></addata></record>
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subjects Animals
Antibodies, Monoclonal - metabolism
APOBEC-3G Deaminase - genetics
APOBEC-3G Deaminase - immunology
APOBEC-3G Deaminase - metabolism
CD4-Positive T-Lymphocytes - immunology
Cell Differentiation
Cell Line
Cell Nucleus - metabolism
Dendritic Cells - cytology
Humans
Immunoprecipitation
Lymphocyte Activation - immunology
Mice, Inbred BALB C
Molecular Weight
Monocytes - cytology
Protein Binding
RNA, Messenger - genetics
RNA, Messenger - metabolism
Subcellular Fractions - enzymology
Up-Regulation - genetics
title Increased expression with differential subcellular location of cytidine deaminase APOBEC3G in human CD4+ T‐cell activation and dendritic cell maturation
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