Linked Life Data

14583461

Source:http://linkedlifedata.com/resource/pubmed/id/14583461

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2003-10-29
pubmed:abstractText
Histone modification enables the ordered regulation of DNA-related processes. Here, we ask if p53, which interacts with histone modifying complexes in vivo, influences histone H3 modification. For this purpose, we compared isogenic clones of human p53+/+ and p53-/- cells in which it is reasonable to attribute any observed differences in histone modification to p53-related effects. Cell growth and cell cycle analyses indicated equivalent proliferation rates for the p53+/+ and p53-/- cell clones. Modification of histone H3 was determined under normal cell growth conditions and also after UV irradiation and/or treatment with trichostatin A (TSA) or nicotinamide (two inhibitors of histone deacetylation). Site-specific histone H3 modifications were determined by immunoblotting. We provide evidence that p53 influences histone H3 acetylation at lysine 9 (K9) and K14, whereas acetylation of K18 appears to be p53 independent. The most striking p53-related effects are at K9, which is underacetylated in p53-/- cells under normal conditions of growth but which shows a dramatic increase in acetylation after combined treatment with UV plus TSA. Conversely, phosphorylation of serine 10 (S10P) is elevated in p53-/- cells and reduced after UV plus TSA treatment. Similar reciprocity between K9Ac and S10P was not evident in p53+/+ cells. Abnormal S10P in p53-/- cells was also observed under completely different experimental conditions where cells were treated with nocodazole to induce G(2)-M arrest and elevation of S10P (which is linked with G(2)-M of the cell cycle). On removal of nocodazole, the p53+/+ cells exhibited rapid reduction in S10P levels and cell cycle recovery. In contrast, the p53-/- cells retained elevated S10P levels and failed to show normal cell cycle recovery. Phosphorylation of S10 is known to be linked with the initiation of chromosome condensation in G(2) and is also important for proper chromosome segregation at mitosis. Our results indicate that loss of p53, directly or indirectly, perturbs the normal regulation of S10 phosphorylation. We suggest that this effect may contribute toward the development of abnormal chromosomes and aneuploidy in p53-deficient cancers.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6674-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Loss of p53 has site-specific effects on histone H3 modification, including serine 10 phosphorylation important for maintenance of ploidy.
pubmed:affiliation
Yorkshire Cancer Research p53 Research Group, Department of Biology, University of York, York YO10 5DD, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't