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

C. Rathinam, Christine Thien, Wallace Langdon, H. Gu, R.A. Flavell

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)992-997
JournalGenes & development
Volume22
Issue number8
DOIs
Publication statusPublished - 2008

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