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論文
- タイトル
- タイトル（英）
- SLFN11-mediated ribosome biogenesis impairment induces TP53-independent apoptosis.
- 参照URL
- https://researchmap.jp/7000009079/published_papers/49094658
- 著者
- 著者（英）
- Akane Ogawa,Keiichi Izumikawa,Sota Tate,Sho Isoyama,Masaru Mori,Kohei Fujiwara,Soyoka Watanabe,Takayuki Ohga,Ukhyun Jo,Daiki Taniyama,Shojiro Kitajima,Soichiro Tanaka,Hiroshi Onji,Shun-Ichiro Kageyama,Gaku Yamamoto,Hitoshi Saito,Tomoko Yamamori Morita,Masayasu Okada,Manabu Natsumeda,Masami Nagahama,Junya Kobayashi,Akihiro Ohashi,Hiroyuki Sasanuma,Shigeki Higashiyama,Shingo Dan,Yves Pommier,Junko Murai
- 担当区分
- 概要
- 概要（英）
- Impairment of ribosome biogenesis (RiBi) triggered by inhibition of ribosomal RNA (rRNA) synthesis and processing leads to various biological effects. We report that Schlafen 11 (SLFN11) induces TP53-independent apoptosis through RiBi impairment. Upon replication stress, SLFN11 inhibits rRNA synthesis with RNA polymerase I accumulation and increased chromatin accessibility in the ribosomal DNA (rDNA) genes. SLFN11-dependent RiBi impairment preferentially depletes short-lived proteins, particularly MCL1, leading to apoptosis in response to replication stress. SLFN11's Walker B motif (E669), DNA-binding site (K652), dephosphorylation site for single-strand DNA binding (S753), and RNase sites (E209/E214) are all required for the SLFN11-mediated RiBi impairment. Comparable effects were obtained with direct RNA polymerase I inhibitors and other RiBi inhibitory conditions regardless of SLFN11. These findings were extended across 34 diverse human cancer cell lines. Thus, we demonstrate that RiBi impairment is a robust inactivator of MCL1 and an additional proapoptotic mechanism by which SLFN11 sensitizes cancer cells to chemotherapeutic agents.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Molecular cell
- 巻
- 号
- 開始ページ
- 終了ページ
- 出版年月
- 2025年1月30日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1016/j.molcel.2025.01.008
- 共同研究・競争的資金等の研究課題
研究者
笹沼 博之
( )