Histone deacetylase inhibitors suppress IFNalpha-induced up-regulation of promyelocytic leukemia protein
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
17062732
DOI
10.1182/blood-2006-02-003418
PII: S0006-4971(20)41975-5
Knihovny.cz E-zdroje
- MeSH
- aktivace transkripce účinky léků MeSH
- inhibitory enzymů farmakologie MeSH
- inhibitory histondeacetylas * MeSH
- interferon alfa farmakologie MeSH
- jaderné proteiny genetika MeSH
- kultivované buňky MeSH
- lidé MeSH
- nádorové buňky kultivované MeSH
- nádorové proteiny genetika MeSH
- nádorové supresorové proteiny genetika MeSH
- protein promyelocytické leukemie MeSH
- RNA nádorová analýza MeSH
- transkripční faktor STAT2 metabolismus MeSH
- transkripční faktory genetika MeSH
- upregulace účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- inhibitory enzymů MeSH
- inhibitory histondeacetylas * MeSH
- interferon alfa MeSH
- jaderné proteiny MeSH
- nádorové proteiny MeSH
- nádorové supresorové proteiny MeSH
- PML protein, human MeSH Prohlížeč
- protein promyelocytické leukemie MeSH
- RNA nádorová MeSH
- transkripční faktor STAT2 MeSH
- transkripční faktory MeSH
Promyelocytic leukemia nuclear bodies (PML NBs), the structural domains of the eukaryotic cell nucleus, play a role in cancer and apoptosis, and their involvement in antiviral mechanisms mediated by interferons (IFNs) is proposed. IFNs dramatically increase the transcription of the PML gene. In this study, we have shown that the response of 2 structural PML NB components, PML and Sp100, to interferon-alpha (IFNalpha) was suppressed in cells simultaneously treated with histone deacetylase (HDAC) inhibitors (trichostatin A, sodium butyrate, MS-275, SAHA, and valproic acid). Trichostatin A (TSA) blocked the increase of PML NB number and suppressed up-regulation of PML mRNA and protein levels in several human cell lines and in normal diploid skin fibroblasts. Moreover, IFNalpha induction of IRF-1 was also inhibited by TSA, although incompletely. Analysis of cellular fractions did not show any defects in cytoplasmic-nuclear transport of STAT2, a component of transcription factor ISGF3 responsible for IFNalpha/beta-dependent gene transcription. Moreover, chromatin immunoprecipitation showed that after IFNalpha stimulation STAT2 binds to ISRE element of PML promoter even in the presence of TSA and thus excluded STAT2-dependent mechanism of TSA effect. These results indicate that the action of histone deacetylases is necessary for the full transcriptional activation of IFNalpha-stimulated genes.
Blood. 2007 Jun 1;109(11):4606 PubMed
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