Linked Life Data

17822787

Source:http://linkedlifedata.com/resource/pubmed/id/17822787

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9-10
pubmed:dateCreated
2007-9-21
pubmed:abstractText
HEC1 (highly expressed in cancer), which localizes to kinetochore in cell mitosis, plays an essential role in chromosome segregation for M phase progression. To clarify the mechanism of its transcriptional regulation, we searched out and isolated its 5'-flanking region. Mapping of this region identified that it is a TATA-less promoter and contains several putative binding sites for different transcription factors. The results from HeLa cells transfected with pGL3 luciferase reporter vectors containing progressive deletion of the HEC1 5'-flanking region demonstrated that two elements containing binding sites for cAMP responsive element binding (CREB) protein and activating transcription factor 4 (ATF4 or CREB2) are critical for transcriptional activity. Mutation of the two elements, not downstream E2F box, resulted in a significant reduction of the promoter activity. Gel shift and supershift assays also demonstrated specific binding of transcription factors to their putative binding sites. Furthermore, overexpression of either CREB or ATF4 enhanced the activation of the HEC1 promoter and overexpression of both of them had an additive effect on the activation of the HEC1 transcription. Conversely, overexpression of dominant negative mutants of either CREB or ATF4 resulted in downregulation of HEC1 mRNA significantly. Our study provided a new insight into a potential mechanism of how transcription factors of CREB family are involved in the regulation of kinetochore protein HEC1 in cancer-related cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:volume
1769
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
593-602
pubmed:dateRevised
2008-5-7
pubmed:meshHeading
pubmed:articleTitle
Functional characterization of the promoter of human kinetochore protein HEC1: novel link between regulation of the cell cycle protein and CREB family transcription factors.
pubmed:affiliation
Anhui Province Key Laboratory of Molecular Medicine, School of Life Science, University of Science and Technology of China, Hefei, Anhui, 230027, China. charlson@ustc.edu.cn
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't