Linked Life Data

7961944

Source:http://linkedlifedata.com/resource/pubmed/id/7961944

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
47
pubmed:dateCreated
1994-12-28
pubmed:abstractText
Clone 112 cells, a rat embryo fibroblast cell line cotransfected by an activated ras gene and a temperature-sensitive mutant p53 gene (p53val135) grow well at 37 degrees C but cease DNA synthesis and cell division when shifted to 32 degrees C (Michalovitz, D., Halevy, O., and Oren, M. (1990) Cell 62, 671-680). Characterization of the p53 protein in exponentially growing clone 112 cells at 37 degrees C revealed that both wild-type (reactive with the monoclonal antibody PAb 246) and mutant (reactive with PAb 240) p53 conformational forms are co-expressed. These results indicate that in clone 112 cells the growth suppressor activity of the wild-type p53 species is inactivated at 37 degrees C. We show that clone 112 cells grown at 37 degrees C elicits specific growth inhibition response to stimulation by the tumor promoter phorbol ester, phorbol 12-myristate 13-acetate (PMA). At 37 degrees C, PMA induced nuclear accumulation of the p53 protein, a behavior that is also observed in growth-arrested cells at 32 degrees C. Furthermore, when cells are growth arrested at 32 degrees C, PMA prevented the cells from re-entering the cell cycle when they are shifted back to 37 degrees C. All these observations suggest that PMA can cooperate with the wild-type p53 in cell growth arrest. At 37 and 32 degrees C, PMA stimulation of clone 112 cells resulted in specific enhancement of phosphorylation of the wild-type p53 species but not of the mutant form. We also demonstrate that the growth arrest of clone 112 cells at 37 degrees C is correlated with stimulation of the nuclear wild-type p53-DNA binding activities. The PMA-mediated increase in p53 DNA binding activity coincides with the loss of the PAb 421 epitope on the p53.DNA complex. PAb 421 non-reactivity with p53 has been shown by others to occur in growth-arrested cells and upon phosphorylation of p53 by protein kinase C. We also provide evidence that, in vitro, the protein kinase C mode of phosphorylation stimulates DNA binding activities of purified recombinant wild-type p53 and that in a mutant conformation p53 is not a substrate for protein kinase C. We propose that wild-type p53 and protein kinase C, the cellular receptor of phorbol ester, could participate in the negative feedback controls associated with the phosphoinositide-derived signals common to a number of mitogenic stimulations.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
269
pubmed:geneSymbol
ras
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29579-87
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:7961944-Animals, pubmed-meshheading:7961944-Biological Transport, pubmed-meshheading:7961944-Cell Division, pubmed-meshheading:7961944-Cell Line, Transformed, pubmed-meshheading:7961944-Cell Nucleus, pubmed-meshheading:7961944-Clone Cells, pubmed-meshheading:7961944-DNA-Binding Proteins, pubmed-meshheading:7961944-Embryo, Mammalian, pubmed-meshheading:7961944-Enzyme Activation, pubmed-meshheading:7961944-Fibroblasts, pubmed-meshheading:7961944-Genes, ras, pubmed-meshheading:7961944-Hot Temperature, pubmed-meshheading:7961944-Mutation, pubmed-meshheading:7961944-Phosphorylation, pubmed-meshheading:7961944-Protein Kinase C, pubmed-meshheading:7961944-Rats, pubmed-meshheading:7961944-Recombinant Proteins, pubmed-meshheading:7961944-Tetradecanoylphorbol Acetate, pubmed-meshheading:7961944-Tumor Suppressor Protein p53
pubmed:year
1994
pubmed:articleTitle
The protein kinase C activator, phorbol ester, cooperates with the wild-type p53 species of Ras-transformed embryo fibroblasts growth arrest.
pubmed:affiliation
Département de Biologie Moléculaire et Structural, INSERM Unité 309, Commissariat à l'Energie Atomique, Grenoble, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't