Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL

Sahoko Matsuoka, Yuichi Oike, Ichiro Onoyama, Atsushi Iwama, Fumio Arai, Keiyo Takubo, Yoichi Mashimo, Hideyuki Oguro, Eriko Nitta, Keisuke Ito, Kana Miyamoto, Hiroki Yoshiwara, Kentaro Hosokawa, Yuka Nakamura, Yumiko Gomei, Hiroko Iwasaki, Yasuhide Hayashi, Yumi Matsuzaki, Keiko Nakayama, Yasuo IkedaAkira Hata, Shigeru Chiba, Keiichi I. Nakayama, Toshio Suda

研究成果: Contribution to journalArticle査読

136 被引用数 (Scopus)

抄録

Common molecular machineries between hematopoietic stem cell (HSC) maintenance and leukemia prevention have been highlighted. The tumor suppressor Fbxw7 (F-box and WD-40 domain protein 7), a subunit of an SCF-type ubiquitin ligase complex, induces the degradation of positive regulators of the cell cycle. We demonstrate that inactivation of Fbxw7 in hematopoietic cells causes premature depletion of HSCs due to active cell cycling and p53-dependent apoptosis. Interestingly, Fbxw7 deletion also confers a selective advantage to cells with suppressed p53 function, eventually leading to development of T-cell acute lymphoblastic leukemia (TALL). Thus, Fbxw7 functions as a fail-safe mechanism against both premature HSC loss and leukemogenesis.

本文言語英語
ページ(範囲)986-991
ページ数6
ジャーナルGenes and Development
22
8
DOI
出版ステータス出版済み - 4 15 2008

All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 発生生物学

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