ID 55299
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Kawaguchi, Yuka Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
Nariki, Hiroaki Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
Kawamoto, Naoko Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
Kanehiro, Yuichi Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
Miyazaki, Satoshi Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
Suzuki, Mari Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
Magari, Masaki Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
Tokumitsu, Hiroshi Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
Kanayama, Naoki Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University ORCID Kaken ID
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.
Keywords
AID
DT40
Gene conversion
Ig
SRSF1
Somatic hypermutation
Published Date
2017-04
Publication Title
Biochemical and Biophysical Research Communications
Volume
volume485
Issue
issue2
Publisher
Elsevier
Start Page
261
End Page
266
ISSN
0006-291X
NCID
AA00564395
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.ja
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isVersionOf https://doi.org/10.1016/j.bbrc.2017.02.097