Linked Life Data

17879942

Source:http://linkedlifedata.com/resource/pubmed/id/17879942

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-4-2
pubmed:abstractText
It is generally accepted that exposure of cells to a variety of DNA-damaging agents leads to up-regulation and activation of wild-type (wt) p53 protein. We investigated the (re)-activation of p53 protein in two human cancer cell lines in which the gene for this tumor suppressor is not mutated: HeLaS(3) cervix carcinoma and MCF-7 breast cancer cells, by induction via different genotoxic and cytotoxic stimuli. Treatment of human cells with the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or different anti-cancer drugs resulted in a strong DNA damage as evidenced by Comet assay and a marked increase in site-specific phosphorylation of H2AX. Unlike in MCF-7 cells, in HeLaS(3) cells the expression of p53 protein did not increase after MNNG treatment despite a strong DNA damage. However, other agents for example doxorubicin markedly induced p53 response in HeLaS(3) cells. After exposure of these cells to MNNG, the ATM-dependent effector proteins Chk2 and NBS1 were phosphorylated, thereby evidencing that MNNG-induced DNA breakage was recognized and properly signaled. In HeLaS(3) cells wt p53 protein is not functional due to E6-mediated targeting for accelerated ubiquitylation and degradation. Therefore, the activation of a p53 response to genotoxic stress in HeLaS(3) cells seems to depend on the status of E6 oncoprotein. Indeed, the induction of p53 protein in HeLaS(3) cells in response to distinct agents inversely correlates with the cellular level of E6 oncoprotein. This implicates that the capability of different agents to activate p53 in HeLaS(3) cells primarily depends on their inhibitory effect on expression of E6 oncoprotein.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic, http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin, http://linkedlifedata.com/resource/pubmed/chemical/Methylnitronitrosoguanidine, http://linkedlifedata.com/resource/pubmed/chemical/NBN protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Viral, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/TP53 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53, http://linkedlifedata.com/resource/pubmed/chemical/checkpoint kinase 2
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1097-4644
pubmed:author
pubmed:copyrightInfo
2007 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1607-20
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Signaling of DNA damage is not sufficient to induce p53 response: (re)activation of wt p53 protein strongly depends on cellular context.
pubmed:affiliation
Cell Cycle Regulation Group, Department of Medicine I, Division: Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8 a, A-1090 Vienna, Austria. Jozefa.Gadek-Wesierski@meduniwien.ac.at
pubmed:publicationType
Journal Article