期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 31, 期 13, 页码 2544-2551出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.01458-10
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资金
- Vanderbilt-Ingram Cancer Center [P30CA68485]
- Vanderbilt Digestive Diseases Research Center [5P30DK58404]
- National Institutes of Health (NIH) [R01-CA64140, R01-HL088494, F30 HL093993]
Mtg16/Eto2 is a transcriptional corepressor that is disrupted by t(16; 21) in acute myeloid leukemia. Using mice lacking Mtg16, we found that Mtg16 is a critical regulator of T-cell development. Deletion of Mtg16 led to reduced thymocyte development in vivo, and after competitive bone marrow transplantation, there was a nearly complete failure of Mtg16(-/-) cells to contribute to thymocyte development. This defect was recapitulated in vitro as Mtg16(-/-) Lineage(-)/Sca1(+)/c-Kit(+) (LSK) cells of the bone marrow or DN1 cells of the thymus failed to produce CD4(+)/CD8(+) cells in response to a Notch signal. Complementation of these defects by reexpressing Mtg16 showed that 3 highly conserved domains were somewhat dispensable for T-cell development but required the capacity of Mtg16 to suppress E2A-dependent transcriptional activation and to bind to the Notch intracellular domain. Thus, Mtg16 integrates the activities of signaling pathways and nuclear factors in the establishment of T-cell fate specification.
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