Transcriptional repression of the microphthalmia gene in melanoma cells correlates with the unresponsiveness of target genes to ectopic microphthalmia-associated transcription factor
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
11886515
DOI
10.1046/j.0022-202x.2001.01563.x
PII: S0022-202X(15)41489-7
Knihovny.cz E-zdroje
- MeSH
- buněčné dělení genetika MeSH
- DNA vazebné proteiny chemie genetika farmakologie MeSH
- fungální proteiny genetika MeSH
- genetická transkripce fyziologie MeSH
- genetické markery MeSH
- intramolekulární oxidoreduktasy genetika MeSH
- lidé MeSH
- melanocyty cytologie fyziologie MeSH
- melanom * MeSH
- membránové glykoproteiny * MeSH
- nádorové buňky kultivované MeSH
- nádory kůže * MeSH
- oxidoreduktasy * MeSH
- peptidové fragmenty metabolismus farmakologie MeSH
- proteiny genetika MeSH
- regulace genové exprese u nádorů fyziologie MeSH
- Saccharomyces cerevisiae - proteiny * MeSH
- terciární struktura proteinů genetika MeSH
- transkripční faktor spojený s mikroftalmií MeSH
- transkripční faktory genetika MeSH
- tyrosinasa genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA vazebné proteiny MeSH
- dopachrome isomerase MeSH Prohlížeč
- fungální proteiny MeSH
- GAL4 protein, S cerevisiae MeSH Prohlížeč
- genetické markery MeSH
- intramolekulární oxidoreduktasy MeSH
- membránové glykoproteiny * MeSH
- MITF protein, human MeSH Prohlížeč
- oxidoreduktasy * MeSH
- peptidové fragmenty MeSH
- proteiny MeSH
- Saccharomyces cerevisiae - proteiny * MeSH
- transkripční faktor spojený s mikroftalmií MeSH
- transkripční faktory MeSH
- tyrosinasa MeSH
- tyrosinase-related protein-1 MeSH Prohlížeč
- TYRP1 protein, human MeSH Prohlížeč
In the melanocyte, expression of genes required for pigment formation is mediated by the microphthalmia transcription factor, which is also critical for the development and survival of normal melanocytes during embryogenesis. Here we show that the expression of the melanocyte-specific isoform of microphthalmia transcription factor is lost in a subset of human melanoma cell lines, accompanied by the repression of tyrosinase and tyrosinase-related proteins 1 and 2, the three transcriptional target genes for microphthalmia. After the forced expression of microphthalmia transcription factor in melanoma cells where the expression of endogenous microphthalmia gene was found to be extinguished, no restoration of the melanogenic phenotype occurred and the transcription of the three microphthalmia transcription factor target genes remained silent. The transcription activation domain of microphthalmia transcription factor, tested as a GAL-MITF fusion protein, remained fully functional in these cells, however, and ectopic microphthalmia transcription factor localized normally to the nucleus and bound to the tyrosinase initiator E-box in gel retardation assays. Thus, the block of differentiation in microphthalmia-transcription-factor-negative melanomas extended the transcriptional repression of the microphthalmia transcription factor gene alone, and endogenous promoters in these melanoma cells became no longer responsive to microphthalmia transcription factor when this was substituted exogenously. The data presented suggest that a specific nuclear context is required for the transcriptional activation of the melanocyte markers by the microphthalmia transcription factor in malignant melanocytes and this specificity is lost concomitantly with the transcriptional repression of microphthalmia transcription factor.
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