共 69 条
Somatic hypermutation is limited by CRM1-dependent nuclear export of activation-induced deaminase
被引:175
作者:

McBride, KM
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机构: Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA

Barreto, V
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机构: Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA

Ramiro, AR
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h-index: 0
机构: Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA

Stavropoulos, P
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h-index: 0
机构: Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA

Nussenzweig, MC
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h-index: 0
机构: Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA
机构:
[1] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA
[2] Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA
关键词:
somatic hypermutation;
activation-induced deaminase;
nucleo-cytoplasmic trasnport;
B lymphocytes;
Ig class switching;
D O I:
10.1084/jem.20040373
中图分类号:
R392 [医学免疫学];
Q939.91 [免疫学];
学科分类号:
100102 ;
摘要:
Somatic hypermutation (SHM) and class switch recombination (CSR) are initiated in activated B lymphocytes by activation-induced deaminase (AID). AID is thought to make lesions in DNA by deaminating cytidine residues in single-stranded DNA exposed by RNA polymerase during, transcription. Although this must occur in the nucleus, AID is found primarily in the cytoplasm. Here we show that AID is actively excluded from the nucleus by an exportin CRM1-dependent pathway. The AID nuclear export signal (NES) is found at the carboxyl terminus of AID in a region that overlaps a sequence required for CSR but not SHM. We find that AID lacking a functional NES causes more hypermutation ora nonphysiologic target gene in transfected fibroblasts. However, the NES does not impact on the rate of mutation of immunoglobulin genes in B lymphocytes, suggesting that the AID NES does not limit AID activity in these cells.
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页码:1235 / 1244
页数:10
相关论文
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