TY - JOUR
T1 - Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL
AU - Matsuoka, Sahoko
AU - Oike, Yuichi
AU - Onoyama, Ichiro
AU - Iwama, Atsushi
AU - Arai, Fumio
AU - Takubo, Keiyo
AU - Mashimo, Yoichi
AU - Oguro, Hideyuki
AU - Nitta, Eriko
AU - Ito, Keisuke
AU - Miyamoto, Kana
AU - Yoshiwara, Hiroki
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
PY - 2008/4/15
Y1 - 2008/4/15
N2 - 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.
AB - 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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U2 - 10.1101/gad.1621808
DO - 10.1101/gad.1621808
M3 - Article
C2 - 18367647
AN - SCOPUS:42149132696
VL - 22
SP - 986
EP - 991
JO - Genes and Development
JF - Genes and Development
SN - 0890-9369
IS - 8
ER -