| pubmed-article:16951198 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:16951198 | lifeskim:mentions | umls-concept:C0215848 | lld:lifeskim |
| pubmed-article:16951198 | lifeskim:mentions | umls-concept:C0332281 | lld:lifeskim |
| pubmed-article:16951198 | lifeskim:mentions | umls-concept:C2003941 | lld:lifeskim |
| pubmed-article:16951198 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:16951198 | lifeskim:mentions | umls-concept:C2718090 | lld:lifeskim |
| pubmed-article:16951198 | pubmed:issue | 17 | lld:pubmed |
| pubmed-article:16951198 | pubmed:dateCreated | 2006-9-4 | lld:pubmed |
| pubmed-article:16951198 | pubmed:abstractText | Hypoxia-inducible factor 1 alpha (HIF-1 alpha) plays a critical role in transcriptional gene activation involved in tumor angiogenesis. A novel class of agents, the histone deacetylase (HDAC) inhibitors, has been shown to inhibit tumor angiogenesis and HIF-1 alpha protein expression. However, the molecular mechanism responsible for this inhibition remains to be elucidated. In the current study, we investigated the molecular link between HIF-1 alpha inhibition and HDAC inhibition. Treatment of the VHL-deficient human renal cell carcinoma cell line UMRC2 with the hydroxamic HDAC inhibitor LAQ824 resulted in a dose-dependent inhibition of HIF-1 alpha protein via a VHL-independent mechanism and reduction of HIF-1 alpha transcriptional activity. HIF-1 alpha inhibition by LAQ824 was associated with HIF-1 alpha acetylation and polyubiquitination. HIF-1 alpha immunoprecipitates contained HDAC activity. Then, we tested different classes of HDAC inhibitors with diverse inhibitory activity of class I versus class II HDACs and assessed their capability of targeting HIF-1 alpha. Hydroxamic acid derivatives with known activity against both class I and class II HDACs were effective in inhibiting HIF-1 alpha at low nanomolar concentrations. In contrast, valproic acid and trapoxin were able to inhibit HIF-1 alpha only at concentrations that are effective against class II HDACs. Coimmunoprecipitation studies showed that class II HDAC4 and HDAC6 were associated with HIF-1 alpha protein. Inhibition by small interfering RNA of HDAC4 and HDAC6 reduced HIF-1 alpha protein expression and transcriptional activity. Taken together, these results suggest that class II HDACs are associated with HIF-1 alpha stability and provide a rationale for targeting HIF-1 alpha with HDAC inhibitors against class II isozymes. | lld:pubmed |
| pubmed-article:16951198 | pubmed:language | eng | lld:pubmed |
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| pubmed-article:16951198 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:16951198 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16951198 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:16951198 | pubmed:issn | 1538-7445 | lld:pubmed |
| pubmed-article:16951198 | pubmed:author | pubmed-author:AtadjaPeterP | lld:pubmed |
| pubmed-article:16951198 | pubmed:author | pubmed-author:VerheulHenk... | lld:pubmed |
| pubmed-article:16951198 | pubmed:author | pubmed-author:CarducciMicha... | lld:pubmed |
| pubmed-article:16951198 | pubmed:author | pubmed-author:PiliRobertoR | lld:pubmed |
| pubmed-article:16951198 | pubmed:author | pubmed-author:CollisSpencer... | lld:pubmed |
| pubmed-article:16951198 | pubmed:author | pubmed-author:QianDavid ZDZ | lld:pubmed |
| pubmed-article:16951198 | pubmed:author | pubmed-author:KachhapSushan... | lld:pubmed |
| pubmed-article:16951198 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:16951198 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:16951198 | pubmed:volume | 66 | lld:pubmed |
| pubmed-article:16951198 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16951198 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16951198 | pubmed:pagination | 8814-21 | lld:pubmed |
| pubmed-article:16951198 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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| pubmed-article:16951198 | pubmed:year | 2006 | lld:pubmed |
| pubmed-article:16951198 | pubmed:articleTitle | Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha. | lld:pubmed |
| pubmed-article:16951198 | pubmed:affiliation | The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA. | lld:pubmed |
| pubmed-article:16951198 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:16951198 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
| pubmed-article:16951198 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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