Linked Life Data

11358490

Source:http://linkedlifedata.com/resource/pubmed/id/11358490

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2001-5-18
pubmed:abstractText
In unstressed cells, the tumor suppressor protein p53 is present in a latent state and is maintained at low levels through targeted degradation. A variety of genotoxic stresses initiate signaling pathways that transiently stabilize the p53 protein, cause it to accumulate in the nucleus, and activate it as a transcription factor. Activation leads either to growth arrest at the G1/S or G2/M transitions of the cell cycle or to apoptosis. Recent studies point to roles for multiple post-translational modifications in mediating these events in response to genotoxic stresses through several potentially interacting but distinct pathways. The approximately 100 amino-acid N-terminal and approximately 90 amino-acid C-terminal domains are highly modified by post-translational modifications. The N-terminus is heavily phosphorylated while the C-terminus contains phosphorylated, acetylated and sumoylated residues. Antibodies that recognize p53 only when it has been modified at specific sites have been developed, and studies with these reagents show that most known post-translational modifications are induced when cells are exposed to genotoxic stresses. These recent results, coupled with biochemical and genetic studies, suggest that N-terminal phosphorylations are important for stabilizing p53 and are crucial for acetylation of C-terminal sites, which in combination lead to the full p53-mediated response to genotoxic stresses. Modifications to the C-terminus inhibit the ability of this domain to negatively regulate sequence-specific DNA binding; additionally, they modulate the stability, the oligomerization state, the nuclear import/export process and the degree of ubiquitination of p53.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0014-2956
pubmed:author
pubmed:issnType
Print
pubmed:volume
268
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2764-72
pubmed:dateRevised
2007-7-23
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Post-translational modifications and activation of p53 by genotoxic stresses.
pubmed:affiliation
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. ea3v@nih.gov
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Review