RRC ID 52109
著者 Kawaguchi Y, Nariki H, Kawamoto N, Kanehiro Y, Miyazaki S, Suzuki M, Magari M, Tokumitsu H, Kanayama N.
タイトル SRSF1-3 contributes to diversification of the immunoglobulin variable region gene by promoting accumulation of AID in the nucleus.
ジャーナル Biochem Biophys Res Commun
Abstract Activation-induced cytidine deaminase (AID) is essential for diversification of the Ig variable region (IgV). AID is excluded from the nucleus, where it normally functions. However, the molecular mechanisms responsible for regulating AID localization remain to be elucidated. The SR-protein splicing factor SRSF1 is a nucleocytoplasmic shuttling protein, a splicing isoform of which called SRSF1-3, has previously been shown to contribute to IgV diversification in chicken DT40 cells. In this study, we examined whether SRSF1-3 functions in IgV diversification by promoting nuclear localization of AID. AID expressed alone was localized predominantly in the cytoplasm. In contrast, co-expression of AID with SRSF1-3 led to the nuclear accumulation of both AID and SRSF1-3 and the formation of a protein complex that contained them both, although SRSF1-3 was dispensable for nuclear import of AID. Expression of either SRSF1-3 or a C-terminally-truncated AID mutant increased IgV diversification in DT40 cells. However, overexpression of exogenous SRSF1-3 was unable to further enhance IgV diversification in DT40 cells expressing the truncated AID mutant, although SRSF1-3 was able to form a protein complex with the AID mutant. These results suggest that SRSF1-3 promotes nuclear localization of AID probably by forming a nuclear protein complex, which might stabilize nuclear AID and induce IgV diversification in an AID C-terminus-dependent manner.
巻・号 485(2)
ページ 261-266
公開日 2017-4-1
DOI 10.1016/j.bbrc.2017.02.097
PII S0006-291X(17)30390-X
PMID 28235482
MeSH Active Transport, Cell Nucleus Animals Avian Proteins / genetics* Avian Proteins / metabolism* Cell Line Cell Nucleus / genetics Cell Nucleus / metabolism Chickens / genetics* Chickens / metabolism Cytidine Deaminase / metabolism* Gene Conversion Immunoglobulin Variable Region / genetics* Serine-Arginine Splicing Factors / metabolism* Somatic Hypermutation, Immunoglobulin*
IF 2.985
引用数 3
リソース情報
ヒト・動物細胞 DT40(RCB1464) 293T(RCB2202)