Linked Life Data

17464181

Source:http://linkedlifedata.com/resource/pubmed/id/17464181

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-4-27
pubmed:abstractText
The BubR1 mitotic-checkpoint protein monitors proper attachment of microtubules to kinetochores, and links regulation of chromosome-spindle attachment to mitotic-checkpoint signaling. Thus, disruption of BubR1 activity results in a loss of checkpoint control, chromosomal instability caused by a premature anaphase, and/or the early onset of tumorigenesis. The mechanisms by which deregulation and/or abnormalities of BubR1 expression operate, however, remain to be elucidated. In this study, we demonstrate that levels of BubR1 expression are significantly increased by demethylation. Bisulfite sequencing analysis revealed that the methylation status of two CpG sites in the essential BubR1 promoter appear to be associated with BubR1 expression levels. Associations of MBD2 and HDAC1 with the BubR1 promoter were significantly relieved by addition of 5-aza-2'-deoxycytidine, an irreversible DNA methyltransferase inhibitor. However, genomic DNA isolated from 31 patients with colorectal carcinomas exhibited a +84A/G polymorphic change in approximately 60% of patients, but this polymorphism had no effect on promoter activity. Our findings indicate that differential regulation of BubR1 expression is associated with changes in BubR1 promoter hypermethylation patterns, but not with promoter polymorphisms, thus providing a novel insight into the molecular regulation of BubR1 expression in human cancer cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1226-3613
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
195-204
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17464181-Azacitidine, pubmed-meshheading:17464181-Base Sequence, pubmed-meshheading:17464181-Cell Line, Tumor, pubmed-meshheading:17464181-DNA Methylation, pubmed-meshheading:17464181-DNA Mutational Analysis, pubmed-meshheading:17464181-DNA-Binding Proteins, pubmed-meshheading:17464181-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17464181-HeLa Cells, pubmed-meshheading:17464181-Histone Deacetylase 1, pubmed-meshheading:17464181-Histone Deacetylases, pubmed-meshheading:17464181-Humans, pubmed-meshheading:17464181-Jurkat Cells, pubmed-meshheading:17464181-Molecular Sequence Data, pubmed-meshheading:17464181-Neoplasms, pubmed-meshheading:17464181-Polymorphism, Genetic, pubmed-meshheading:17464181-Promoter Regions, Genetic, pubmed-meshheading:17464181-Protein Binding, pubmed-meshheading:17464181-Protein Kinases, pubmed-meshheading:17464181-Protein-Serine-Threonine Kinases, pubmed-meshheading:17464181-Transcription, Genetic
pubmed:year
2007
pubmed:articleTitle
Differential promoter methylation may be a key molecular mechanism in regulating BubR1 expression in cancer cells.
pubmed:affiliation
Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't