Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
23
|
| pubmed:dateCreated |
1997-7-24
|
| pubmed:abstractText |
The c-Myc protein strongly stimulates cellular proliferation, inducing cells to exit G0/G1 and enter the cell cycle. At a molecular level, Myc prevents growth arrest and drives cell cycle progression through the transcriptional regulation of Myc-target genes. Expression of the growth arrest and DNA damage inducible gene 45 (gadd45) is elevated in response to DNA damaging agents, such as ionizing radiation via a p53-dependent mechanism, upon nutrient deprivation, or during differentiation. Gadd45 holds a vital role in growth arrest as ectopic expression confers a strong block to proliferation. Exposure of quiescent cells to mitogen stimulates a rapid increase in c-Myc expression which is followed by the subsequent reduction in gadd45 expression. The kinetics of these two regulatory events suggest that Myc suppresses the expression of gadd45, contributing to G0/G1 phase exit of the cell cycle. Indeed, ectopic Myc expression in primary and immortalized fibroblasts results in the suppression of gadd45 mRNA levels, by a mechanism which is independent of cell cycle progression. Using an inducible MycER system, rapid suppression of gadd45 mRNA is first evident approximately 0.5 h following Myc activation. The reduction in gadd45 mRNA expression occurs at the transcriptional level and is mediated by a p53-independent pathway. Moreover, Myc suppression and p53 induction of gadd45 following exposure to ionizing radiation are non-competitive co-regulatory events. Myc suppression of gadd45 defines a novel pathway through which Myc promotes cell cycle entry and prevents growth arrest of transformed cells.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/GADD45 protein,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0950-9232
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
12
|
| pubmed:volume |
14
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2825-34
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:9190899-Animals,
pubmed-meshheading:9190899-Binding Sites,
pubmed-meshheading:9190899-Blood,
pubmed-meshheading:9190899-Cells, Cultured,
pubmed-meshheading:9190899-DNA Damage,
pubmed-meshheading:9190899-Fibroblasts,
pubmed-meshheading:9190899-Gene Expression Regulation,
pubmed-meshheading:9190899-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:9190899-Kinetics,
pubmed-meshheading:9190899-Mice,
pubmed-meshheading:9190899-Models, Molecular,
pubmed-meshheading:9190899-Promoter Regions, Genetic,
pubmed-meshheading:9190899-Proteins,
pubmed-meshheading:9190899-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:9190899-RNA, Messenger,
pubmed-meshheading:9190899-Rats,
pubmed-meshheading:9190899-Transcription, Genetic,
pubmed-meshheading:9190899-Transcription Factors,
pubmed-meshheading:9190899-Tumor Suppressor Protein p53
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Myc represses the growth arrest gene gadd45.
|
| pubmed:affiliation |
Department of Molecular and Medical Genetics, University of Toronto, Ontario Cancer Institute, Canada.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|