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Increased expression with differential subcellular location of cytidine deaminase APOBEC3G in human CD4+ T-cell activation and dendritic cell maturation
被引:13
作者:
Oliva, Harold
[1
,13
]
Pacheco, Rodrigo
[2
,3
]
Martinez-Navio, Jose M.
[4
,14
]
Rodriguez-Garcia, Marta
[1
,5
,15
]
Naranjo-Gomez, Mar
[6
,16
,17
]
Climent, Nuria
[1
]
Prado, Carolina
[3
]
Gil, Cristina
[1
]
Plana, Montserrat
[1
]
Garcia, Felipe
[1
,7
,8
]
Miro, Jose M.
[1
,7
,8
]
Franco, Rafael
[4
,9
]
Borras, Francesc E.
[10
,11
]
Navaratnam, Naveenan
[12
]
Gatell, Jose M.
[1
,7
,8
]
Gallart, Teresa
[1
,5
]
机构:
[1] Univ Barcelona, Fac Med, Hosp Clin Barcelona, Inst Invest Biomed August Pi i Sunyer IDIBAPS,AID, Barcelona, Spain
[2] Univ Andres Bello, Fac Ciencias Biol, Dept Ciencias Biol, Santiago, Chile
[3] Fdn Ciencia & Vida, Lab Neuroinmunol, Santiago, Chile
[4] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, Barcelona, Spain
[5] Hosp Clin Univ Barcelona, Serv Immunol, Villarroel 170, Barcelona 08036, Spain
[6] Autonomous Univ Barcelona, Inst Invest Germans Trias Pujol, LIRAD Lab Immunobiol Res & Diagnost Applicat, Badalona, Barcelona, Spain
[7] Hosp Clin Barcelona, Infect Dis Serv, Barcelona, Spain
[8] Hosp Clin Barcelona, AIDS Unit, Barcelona, Spain
[9] Inst Salud Carlos III, CIBERNED Ctr Invest Red Enfermedades Neurodegener, Madrid, Spain
[10] Inst Invest Germans Trias & Pujol IGTP, IVECAT Grp, Badalona, Spain
[11] Germans Trias & Pujol Univ Hosp, Serv Nephrol, Badalona, Spain
[12] Imperial Coll London, MRC, Ctr Clin Sci, Hammersmith Hosp Campus, London, England
[13] Veterquim SA, Res & Dev Lab, Santiago, Chile
[14] Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33136 USA
[15] Dartmouth Med Sch, Dept Physiol & Neurobiol, Lebanon, NH USA
[16] Inst Genet Mol Montpellier, UMR 5535, CNRS, Montpellier, France
[17] Univ Montpellier, Montpellier, France
基金:
英国医学研究理事会;
关键词:
IMMUNODEFICIENCY-VIRUS TYPE-1;
MESSENGER-RNA LEVELS;
ALU RETROTRANSPOSITION;
L1;
RETROTRANSPOSITION;
INTRINSIC RESISTANCE;
PRIMARY LYMPHOCYTES;
HIV-1;
REPLICATION;
FAMILY PROTEINS;
EDITING ENZYME;
INFECTION;
D O I:
10.1038/icb.2016.28
中图分类号:
Q2 [细胞生物学];
学科分类号:
071009 ;
090102 ;
摘要:
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.
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页码:689 / 700
页数:12
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