Source:http://linkedlifedata.com/resource/pubmed/id/14961038
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2004-3-26
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| pubmed:abstractText |
The Notch family of transmembrane receptors has been implicated in the regulation of many developmental processes. In this study, we evaluated the role of Notch4 in immature hematopoietic progenitors by inducing, with retroviral transduction, enforced expression of Int-3, the oncogenic and constitutively active form of mouse Notch4. Int-3-transduced human myeloid leukemia (HL-60) cells demonstrated significantly delayed expression of differentiation markers following retinoic acid and 12-0-tetradecanoylphorbol 13-acetate treatment. Furthermore, HL-60 cells expressing Int-3 displayed a slower growth rate than cells infected with void virus, and accumulation in the G0/G1 phases of cell cycle. Transduction with deletion mutants of Int-3 defined the importance of individual domains of the protein (in particular, the ANK domain and the C-terminal domain) in the inhibition of differentiation and growth arrest of HL-60 cells. When mouse bone marrow enriched for stem cells (5-fluorouracil-resistant, lineage negative) was transduced and cultured for two weeks, the Int-3-transduced population displayed a lower expression of differentiation markers and a three- to five-fold higher frequency of colony-forming cells (CFU-GM/BFU-E) than control cultures. These results strongly support the notion that Notch signaling inhibits differentiation and promotes expansion of hematopoietic stem/progenitor cells.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/NOTCH4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phorbol Esters,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Notch,
http://linkedlifedata.com/resource/pubmed/chemical/Tretinoin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
0887-6924
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
18
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
777-87
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:14961038-Animals,
pubmed-meshheading:14961038-Cell Differentiation,
pubmed-meshheading:14961038-Cell Division,
pubmed-meshheading:14961038-Cell Line,
pubmed-meshheading:14961038-HL-60 Cells,
pubmed-meshheading:14961038-Hematopoietic Stem Cells,
pubmed-meshheading:14961038-Humans,
pubmed-meshheading:14961038-Mice,
pubmed-meshheading:14961038-Mice, Inbred BALB C,
pubmed-meshheading:14961038-Myeloid Cells,
pubmed-meshheading:14961038-Myelopoiesis,
pubmed-meshheading:14961038-Phorbol Esters,
pubmed-meshheading:14961038-Protein Structure, Tertiary,
pubmed-meshheading:14961038-Proto-Oncogene Proteins,
pubmed-meshheading:14961038-Receptors, Cell Surface,
pubmed-meshheading:14961038-Receptors, Notch,
pubmed-meshheading:14961038-Transfection,
pubmed-meshheading:14961038-Tretinoin
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| pubmed:year |
2004
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| pubmed:articleTitle |
Expression of constitutively active Notch4 (Int-3) modulates myeloid proliferation and differentiation and promotes expansion of hematopoietic progenitors.
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| pubmed:affiliation |
James Ewing Laboratory of Developmental Hematopoiesis, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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