Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
52
pubmed:dateCreated
1998-1-23
pubmed:abstractText
Cyclin D1 is a critical oncogene involved in the regulation of progression through the G1 phase of the cell cycle, thereby contributing to cell proliferation. This is mediated through interaction of cyclin D1 with its catalytic partners, the cyclin-dependent kinases, and the subsequent phosphorylation of the retinoblastoma protein. Cyclin D1, in turn, is regulated by mitogenic stimuli. We demonstrate that transforming growth factor-alpha (TGFalpha) induces cyclin D1 mRNA in esophageal squamous epithelial cells, and this appears to correlate with increased cyclin D1 protein expression and cyclin-dependent kinase 6 activity. The induction of cyclin D1 transcription by TGFalpha is mediated in part through the induction of the early growth response protein (Egr-1) and its subsequent binding of Egr-1 to a cis-regulatory region spanning nucleotides -144 to -104 of the cyclin D1 promoter. The Egr-1 binding activity to the cyclin D1 promoter appears to require de novo protein synthesis and is not influenced by Sp1 binding to overlapping Sp1 motifs. Taken together, these data provide evidence that TGFalpha enhances cyclin D1 transcription through the induction of Egr-1 binding to a cis-regulatory region in the cyclin D1 promoter. This has important mechanistic implications into the transcriptional regulation of cyclin D1 by an essential proproliferative growth factor and cell cycle progression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CDK6 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 6, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/EGR1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Early Growth Response Protein 1, http://linkedlifedata.com/resource/pubmed/chemical/Early Growth Response..., http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins, http://linkedlifedata.com/resource/pubmed/chemical/KLF10 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Kruppel-Like Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor alpha
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
272
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
33181-90
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9407106-Cyclin D1, pubmed-meshheading:9407106-Cyclin-Dependent Kinase 6, pubmed-meshheading:9407106-Cyclin-Dependent Kinases, pubmed-meshheading:9407106-Cycloheximide, pubmed-meshheading:9407106-DNA-Binding Proteins, pubmed-meshheading:9407106-Early Growth Response Protein 1, pubmed-meshheading:9407106-Early Growth Response Transcription Factors, pubmed-meshheading:9407106-G1 Phase, pubmed-meshheading:9407106-Humans, pubmed-meshheading:9407106-Immediate-Early Proteins, pubmed-meshheading:9407106-Kruppel-Like Transcription Factors, pubmed-meshheading:9407106-Promoter Regions, Genetic, pubmed-meshheading:9407106-Protein Synthesis Inhibitors, pubmed-meshheading:9407106-Protein-Serine-Threonine Kinases, pubmed-meshheading:9407106-RNA, Messenger, pubmed-meshheading:9407106-Restriction Mapping, pubmed-meshheading:9407106-Transcription Factors, pubmed-meshheading:9407106-Transfection, pubmed-meshheading:9407106-Transforming Growth Factor alpha, pubmed-meshheading:9407106-Tumor Cells, Cultured, pubmed-meshheading:9407106-Zinc Fingers
pubmed:year
1997
pubmed:articleTitle
Transforming growth factor-alpha enhances cyclin D1 transcription through the binding of early growth response protein to a cis-regulatory element in the cyclin D1 promoter.
pubmed:affiliation
Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't