MersV1, Main, Exploration, bibRecord, 002737

Cell cycle inhibitor p21/ WAF1/ CIP1 as a cofactor of MITF expression in melanoma cells

Identifieur interne : 002737 ( Main/Exploration ); précédent : 002736; suivant : 002738

Cell cycle inhibitor p21/ WAF1/ CIP1 as a cofactor of MITF expression in melanoma cells

Auteurs : Blanka Šestáková [République tchèque] ; Lubica Ondrušová [République tchèque] ; Jiri Vachtenheim [République tchèque]

Source :

Pigment Cell & Melanoma Research [ 1755-1471 ] ; 2010-04.

RBID : ISTEX:6170A01F18864F39FD632ED593EA099D9EA27579

English descriptors

Teeft :
- Amino acids, Apoptosis, Biol, Cdk2, Cell biol, Cell cycle, Cell extracts, Cell lines, Chem, Cip1, Clone, Coactivates, Cotransfected, Crd1, Crd1 domain, Creb, Cyclin, Derepression, Empty vector, Endogenous, Forskolin, Gapdh, Human melanoma cell lines, John wiley sons, Kinase, Knockdown, Luciferase, Luciferase activity, Malignant, Melanocyte, Melanoma, Melanoma cell lines, Melanoma cells, Melastatin, Mitf, Mitf expression, Mitf mrna, Mitf promoter, Mitf promoter activation, Mitf promoter activity, Mitf protein, Mrna, Mutant, Normal melanocytes, Oncogene, Overexpression, Plasmid, Primer, Promoter, Promoter activity, Protein coactivates mitf promoter, Protein expression, Protein level, Protein levels, Regulator, Regulatory role, Sestakova, Shrna, Transactivation, Transcription, Transcription factor, Transcriptional, Transcriptional repression, Transfected, Tyrosinase, Upper panel, Vachtenheim, Waf1, Western blot, Western blot analysis.

Abstract

p21/ WAF1/ Cip1 (p21), a cyclin‐dependent kinase inhibitor, may act as an antioncogene, but may also behave as a tumor promoting factor by inhibiting apoptosis. p21 is also a transcriptional regulator, exerting this activity independently of cyclin‐dependent kinases. Increased p21 protein levels were found in a subset of melanomas. However, the mechanism(s) contributing to the tolerance of high p21 levels in melanoma cells remains unexplained. Here, we show that the p21 protein positively regulates the promoter of microphthalmia‐associated transcription factor (MITF), a transcription factor which plays a central role in the expression of melanocyte‐specific genes, lineage determination, and survival of melanoma cells. p21 activated the MITF promoter‐reporter, occupied the promoter in vivo and cooperated with cAMP response element binding protein (CREB) in promoter activation. In addition, p21 knockdown by shRNA resulted in a decrease of MITF protein and promoter activity, and p21 protein levels correlated with MITF mRNA in most cell lines tested. As the p21 gene is a known transcriptional target of MITF, the reciprocal stimulation of transcription may constitute a positive‐feedback loop reinforcing MITF expression in melanoma cells. Our results might help explain the tolerance of increased p21 levels found in some melanomas.

Url:

https://api.istex.fr/ark:/67375/WNG-7P01QM1B-8/fulltext.pdf

DOI: 10.1111/j.1755-148X.2010.00670.x

Affiliations:

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Le document en format XML

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<term>Cell cycle</term>
<term>Cell extracts</term>
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<term>Transcriptional repression</term>
<term>Transfected</term>
<term>Tyrosinase</term>
<term>Upper panel</term>
<term>Vachtenheim</term>
<term>Waf1</term>
<term>Western blot</term>
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<front><div type="abstract" xml:lang="en">p21/ WAF1/ Cip1 (p21), a cyclin‐dependent kinase inhibitor, may act as an antioncogene, but may also behave as a tumor promoting factor by inhibiting apoptosis. p21 is also a transcriptional regulator, exerting this activity independently of cyclin‐dependent kinases. Increased p21 protein levels were found in a subset of melanomas. However, the mechanism(s) contributing to the tolerance of high p21 levels in melanoma cells remains unexplained. Here, we show that the p21 protein positively regulates the promoter of microphthalmia‐associated transcription factor (MITF), a transcription factor which plays a central role in the expression of melanocyte‐specific genes, lineage determination, and survival of melanoma cells. p21 activated the MITF promoter‐reporter, occupied the promoter in vivo and cooperated with cAMP response element binding protein (CREB) in promoter activation. In addition, p21 knockdown by shRNA resulted in a decrease of MITF protein and promoter activity, and p21 protein levels correlated with MITF mRNA in most cell lines tested. As the p21 gene is a known transcriptional target of MITF, the reciprocal stimulation of transcription may constitute a positive‐feedback loop reinforcing MITF expression in melanoma cells. Our results might help explain the tolerance of increased p21 levels found in some melanomas.</div>
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Cell cycle inhibitor p21/ WAF1/ CIP1 as a cofactor of MITF expression in melanoma cells

Cell cycle inhibitor p21/ WAF1/ CIP1 as a cofactor of MITF expression in melanoma cells

Source :

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

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