Linked Life Data

20067556

Source:http://linkedlifedata.com/resource/pubmed/id/20067556

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-4-16
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1755-148X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
238-51
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Cell cycle inhibitor p21/ WAF1/ CIP1 as a cofactor of MITF expression in melanoma cells.
pubmed:affiliation
Laboratory of Molecular Biology, University Hospital, Charles University, Prague, Czech Republic.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't