| pubmed-article:15456877 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15456877 | lifeskim:mentions | umls-concept:C0814999 | lld:lifeskim |
| pubmed-article:15456877 | lifeskim:mentions | umls-concept:C0007587 | lld:lifeskim |
| pubmed-article:15456877 | lifeskim:mentions | umls-concept:C0017260 | lld:lifeskim |
| pubmed-article:15456877 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:15456877 | pubmed:issue | 20 | lld:pubmed |
| pubmed-article:15456877 | pubmed:dateCreated | 2004-9-30 | lld:pubmed |
| pubmed-article:15456877 | pubmed:abstractText | The von Hippel-Lindau gene product (pVHL) targets the alpha subunit of basic helix-loop-helix transcription factor hypoxia-inducible factor (HIF) for proteasomal degradation. Inactivation of pVhl in the mouse germ line results in embryonic lethality, indicating that tight control of Hif-mediated adaptive responses to hypoxia is required for normal development and tissue function. In order to investigate the role of pVhl in T-cell development, we generated mice with thymocyte-specific inactivation of Vhlh resulting in constitutive transcriptional activity of Hif-1, as well as mice with thymocyte-specific repression of Hif-1 in a wild-type and Vhlh-deficient background. Thymi from Vhlh-deficient mice were small due to a severe reduction in the total number of CD4/CD8-double-positive thymocytes which was associated with increased apoptosis in vivo and in vitro. Increased apoptosis was a result of enhanced caspase 8 activity, while Bcl-2 and Bcl-XL transgene expression had little effect on this phenotype. Inactivation of Hif-1 in Vhlh-deficient thymocytes restored thymic cellularity as well as thymocyte viability in vitro. Our data suggest that tight regulation of Hif-1 via pVhl is required for normal thymocyte development and viability and that an increase in Hif-1 transcriptional activity enhances caspase 8-mediated apoptosis in thymocytes. | lld:pubmed |
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| pubmed-article:15456877 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:15456877 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:15456877 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15456877 | pubmed:month | Oct | lld:pubmed |
| pubmed-article:15456877 | pubmed:issn | 0270-7306 | lld:pubmed |
| pubmed-article:15456877 | pubmed:author | pubmed-author:JohnsonRandal... | lld:pubmed |
| pubmed-article:15456877 | pubmed:author | pubmed-author:BensingerStev... | lld:pubmed |
| pubmed-article:15456877 | pubmed:author | pubmed-author:TurkaLaurence... | lld:pubmed |
| pubmed-article:15456877 | pubmed:author | pubmed-author:BijuMangatt... | lld:pubmed |
