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 Ikeda; Akira Hata; Shigeru Chiba; Keiichi I. Nakayama; Toshio Suda

doi:10.1101/gad.1621808

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

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145 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	986-991
Number of pages	6
Journal	Genes and Development
Volume	22
Issue number	8
DOIs	https://doi.org/10.1101/gad.1621808
Publication status	Published - Apr 15 2008

All Science Journal Classification (ASJC) codes

Genetics
Developmental Biology

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Matsuoka, S., Oike, Y., Onoyama, I., Iwama, A., Arai, F., Takubo, K., Mashimo, Y., Oguro, H., Nitta, E., Ito, K., Miyamoto, K., Yoshiwara, H., Hosokawa, K., Nakamura, Y., Gomei, Y., Iwasaki, H., Hayashi, Y., Matsuzaki, Y., Nakayama, K., ... Suda, T. (2008). Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL. Genes and Development, 22(8), 986-991. https://doi.org/10.1101/gad.1621808

Matsuoka, S, Oike, Y, Onoyama, I, Iwama, A, Arai, F, Takubo, K, Mashimo, Y, Oguro, H, Nitta, E, Ito, K, Miyamoto, K, Yoshiwara, H, Hosokawa, K, Nakamura, Y, Gomei, Y, Iwasaki, H, Hayashi, Y, Matsuzaki, Y, Nakayama, K, Ikeda, Y, Hata, A, Chiba, S, Nakayama, KI & Suda, T 2008, 'Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL', Genes and Development, vol. 22, no. 8, pp. 986-991. https://doi.org/10.1101/gad.1621808

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abstract = "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.",

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AU - Arai, Fumio

AU - Takubo, Keiyo

AU - Mashimo, Yoichi

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AU - Nitta, Eriko

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AU - Hosokawa, Kentaro

AU - Nakamura, Yuka

AU - Gomei, Yumiko

AU - Iwasaki, Hiroko

AU - Hayashi, Yasuhide

AU - Matsuzaki, Yumi

AU - Nakayama, Keiko

AU - Ikeda, Yasuo

AU - Hata, Akira

AU - Chiba, Shigeru

AU - Nakayama, Keiichi I.

AU - Suda, Toshio

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

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