title: Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL.
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 (T-ALL). Thus, Fbxw7 functions as a fail-safe mechanism against both premature HSC loss and leukemogenesis.
authors: Department of Cell Differentiation, The Sakaguchi Laboratory, School of Medicine, Keio University, Tokyo 160-8582, Japan.
authors: Sahoko
authors: S
authors: Matsuoka
authors: Yuichi
authors: Y
authors: Oike
authors: Ichiro
authors: I
authors: Onoyama
authors: Atsushi
authors: A
authors: Iwama
authors: Fumio
authors: F
authors: Arai
authors: Keiyo
authors: K
authors: Takubo
authors: Yoichi
authors: Y
authors: Mashimo
authors: Hideyuki
authors: H
authors: Oguro
authors: Eriko
authors: E
authors: Nitta
authors: Keisuke
authors: K
authors: Ito
authors: Kana
authors: K
authors: Miyamoto
authors: Hiroki
authors: H
authors: Yoshiwara
authors: Kentaro
authors: K
authors: Hosokawa
authors: Yuka
authors: Y
authors: Nakamura
authors: Yumiko
authors: Y
authors: Gomei
authors: Hiroko
authors: H
authors: Iwasaki
authors: Yasuhide
authors: Y
authors: Hayashi
authors: Yumi
authors: Y
authors: Matsuzaki
authors: Keiko
authors: K
authors: Nakayama
authors: Yasuo
authors: Y
authors: Ikeda
authors: Akira
authors: A
authors: Hata
authors: Shigeru
authors: S
authors: Chiba
authors: Keiichi I
authors: KI
authors: Nakayama
authors: Toshio
authors: T
authors: Suda
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002478:Cells, Cultured; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D000073979:F-Box-WD Repeat-Containing Protein 7; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000201:enzymology*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000201:enzymology / Q000209:etiology*; D051379:Mice; D008822:Mice, Transgenic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513272:Fbxw7 protein, mouse; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases