Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2006-4-13
pubmed:abstractText
FAT10 is a member of the ubiquitin-like modifier family of proteins and has been implicated to play important roles in antigen presentation, cytokine response, apoptosis and mitosis. We have recently demonstrated the upregulation of FAT10 gene expression in 90% of hepatocellular carcinoma patients. Here, we identified and characterized the promoter of the FAT10 gene to elucidate the mechanism of FAT10 gene expression. Notably, we found that the 5' untranslated region (5'UTR), from the transcription start site to 15 bases before the translational start site, displays significant promoter activity. Regions upstream of the 5'UTR (from +26 to -1997) do not confer any promoter activity. Curiously, FAT10 promoter activity and expression is significantly repressed in KB3-1 and HepG2 cells, which have wild-type p53, than in p53-negative Hep3B cells. The role of p53 in regulating FAT10 expression was evident by the significant downregulation (P<0.05) of FAT10 mRNA expression and promoter activity when wild-type p53 was transfected into p53-null Hep3B cells. Conversely, inhibiting p53 expression through siRNA against p53 significantly enhanced FAT10 expression and promoter activity. p53 was found to bind in vivo to the 5' half consensus sequence of p53-binding site located at the FAT10 promoter. Hence, we propose that FAT10 is a downstream target of p53 and dysregulation of FAT10 expression in p53-defective cells could contribute to carcinogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2318-27
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
p53 negatively regulates the expression of FAT10, a gene upregulated in various cancers.
pubmed:affiliation
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't