Linked Life Data

10656682

Source:http://linkedlifedata.com/resource/pubmed/id/10656682

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-2-10
pubmed:abstractText
The activity of the tumor suppressor p53 is induced in response to DNA-damaging agents such as UV and gamma radiation. Phosphorylation is one of the key regulatory steps for activating p53 function. Recent reports have shown that p53 is phosphorylated at both serines 15 and 392 in response to UV radiation. Phosphorylation at serine 15 prevents the binding of HDM2, a negative regulator of p53. Phosphorylation at serine 392 induces the DNA-binding function of p53. We examined the requirement for phosphorylation at both serines and show that both these modifications occur on the same molecule of p53. In vitro assays demonstrate that phosphorylation at either one of these sites is not sufficient to yield an active p53. Phosphorylation by DNA-PK, that modifies serines 15 and 37, inhibits HDM2 binding to p53 but does not induce the DNA-binding activity of p53. Phosphorylation at serine 392, on the other hand, stimulates the DNA-binding ability of p53 but does not make it immune to binding and inhibition by HDM2. Thus, our results demonstrate that multiple sites need to be modified to yield a functional p53.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
358-64
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Cooperative phosphorylation at multiple sites is required to activate p53 in response to UV radiation.
pubmed:affiliation
Department of Molecular Genetics, MD Anderson Cancer Center, Houston, Texas 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.