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タイトル: | APOBEC3B reporter myeloma cell lines identify DNA damage response pathways leading to APOBEC3B expression |
著者: | Yamazaki, Hiroyuki Shirakawa, Kotaro https://orcid.org/0000-0002-7469-1276 (unconfirmed) Matsumoto, Tadahiko Kazuma, Yasuhiro Matsui, Hiroyuki Horisawa, Yoshihito Stanford, Emani Sarca, Anamaria Daniela Shirakawa, Ryutaro Shindo, Keisuke Takaori-Kondo, Akifumi |
著者名の別形: | 山崎, 寛章 白川, 康太郎 松本, 忠彦 数馬, 安浩 松井, 宏行 堀澤, 欣史 白川, 龍太郎 新堂, 啓祐 髙折-近藤, 晃史 |
キーワード: | General Biochemistry, Genetics and Molecular Biology General Agricultural and Biological Sciences General Medicine |
発行日: | 8-Jan-2020 |
出版者: | Public Library of Science (PLoS) |
誌名: | PLOS ONE |
巻: | 15 |
号: | 1 |
論文番号: | e0223463 |
抄録: | Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) DNA cytosine deaminase 3B (A3B) is a DNA editing enzyme which induces genomic DNA mutations in multiple myeloma and in various other cancers. APOBEC family proteins are highly homologous so it is especially difficult to investigate the biology of specifically A3B in cancer cells. To easily and comprehensively investigate A3B function in myeloma cells, we used CRISPR/Cas9 to generate A3B reporter cells that contain 3×FLAG tag and IRES-EGFP sequences integrated at the end of the A3B gene. These reporter cells stably express 3xFLAG tagged A3B and the reporter EGFP and this expression is enhanced by known stimuli, such as PMA. Conversely, shRNA knockdown of A3B decreased EGFP fluorescence and 3xFLAG tagged A3B protein levels. We screened a series of anticancer treatments using these cell lines and identified that most conventional therapies, such as antimetabolites or radiation, exacerbated endogenous A3B expression, but recent molecular targeted therapeutics, including bortezomib, lenalidomide and elotuzumab, did not. Furthermore, chemical inhibition of ATM, ATR and DNA-PK suppressed EGFP expression upon treatment with antimetabolites. These results suggest that DNA damage triggers A3B expression through ATM, ATR and DNA-PK signaling. |
著作権等: | © 2020 Yamazaki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
URI: | http://hdl.handle.net/2433/245660 |
DOI(出版社版): | 10.1371/journal.pone.0223463 |
PubMed ID: | 31914134 |
出現コレクション: | 学術雑誌掲載論文等 |
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