Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1997-12-15
pubmed:abstractText
The mechanisms are poorly understood by which p53 can stimulate different downstream events, including growth arrest, DNA repair, and apoptosis, after DNA damage. Changes in protein levels do not predict a particular p53 response, but it is possible that differences in functional activities such as transactivation are important. The present report describes the successful use of a specific p53 reporter plasmid transfected into primary murine hepatocytes to evaluate p53 transactivation activity over time after two different genotoxic injuries (gamma-irradiation, 15 Gy and UV-c irradiation, 10 J/m2) known to produce p53-dependent growth arrest in this cell type. The results show that UV injury to hepatocytes was followed by a transient increase in transcriptional activation of the reporter plasmid by p53 and that this response preceded changes in p53 protein levels, as assessed by immunocytochemistry. By contrast, gamma-irradiation injury failed to induce detectable changes in either transactivation activity or hepatocyte p53 protein levels. The data show that p53 responses to DNA damage are dependent on both cell and injury type and suggest that in hepatocytes they can be independent of protein concentration and specific transcriptional activity. The results have implications for how particular dysfunctional p53 mutations in carcinogenesis could alter hepatocyte responses to different DNA injuries.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3417
pubmed:author
pubmed:issnType
Print
pubmed:volume
183
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
177-81
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
UV but not gamma-irradiation induces specific transcriptional activity of p53 in primary hepatocytes.
pubmed:affiliation
Sir Alastair Currie Cancer Research Campaign Laboratories, University Department of Pathology, Medical School, Edinburgh, Scotland, U.K.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't