The E3 ubiquitin ligase c-Cbl restricts development and functions of hematopoietic stem cells

被引：89

作者：

Rathinam, Chozhavendan ^{[1
]}

Thien, Christine B. F. ^{[2
]}

Langdon, Wallace Y. ^{[2
]}

Gu, Hua ^{[3
]}

Flavell, Richard A. ^{[1
,4
]}

机构：

[1] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA

[2] Univ Western Australia, Div Pathol, Nedlands, WA 6009, Australia

[3] Columbia Univ, Dept Microbiol, New York, NY 10032 USA

[4] Howard Hughes Med Inst, New Haven, CT 06520 USA

来源：

GENES & DEVELOPMENT | 2008年 / 22卷 / 08期

关键词：

hematopoietic stem cells; c-Cbl; thrombopoietin; STAT5; self-renewal;

D O I：

10.1101/gad.1651408

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Hematopoietic stem cells (HSCs) are multipotent progenitors that give rise to all types of blood cells. In the present study, we document that HSC development and functions are negatively regulated by the E3 ubiquitin ligase c-Cbl (casitas B-cell lymphoma). HSCs of c-Cbl(-/-) mice exhibit augmented pool size, hyperproliferation, greater competence, and enhanced long-term repopulating capacity. Our mechanistic studies identified that c-Cbl(-/-) HSCs are hyperresponsive to thrombopoietin (TPO) and display elevated levels of STAT5 phosphorylation, thus leading to increased c-Myc expression. In essence, our data unequivocally identify c-Cbl as a novel negative regulator of developmental and functional properties of HSCs.

引用

页码：992 / 997

页数：6

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