Linked Life Data

8837616

Source:http://linkedlifedata.com/resource/pubmed/id/8837616

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1996-11-4
pubmed:abstractText
The p53 tumor suppressor protein induces cell-cycle arrest or cell death in response to DNA-damaging agents, such as radiation and many of the chemotherapeutics used in cancer therapy. The function of p53 is dependent on its ability to bind DNA in a sequence-specific manner, but in one-half of all human tumors, its sequence-specific DNA binding domain is compromised by single-amino acid substitutions. The nature of these substitutions, which target residues that directly contact DNA or that stabilize the structure of the DNA binding domain, has raised concerns as to whether the function of p53 mutants could ever be rescued. Nevertheless, pharmaceuticals that restore function to p53 mutants could specifically suppress proliferation of cancer cells in patients. To determine whether tumor-derived p53 mutants are irreversibly inactivated, we introduced basic residues in their DNA binding domains, aiming to establish novel contacts between p53 and the DNA phosphate backbone. In three of the seven most common p53 mutants, replacement of Thr284 with Arg significantly enhanced DNA binding affinity, without affecting DNA binding specificity, and rescued their transactivation and tumor suppressor functions. Thus, many tumor-derived p53 mutants retain their sequence-specific DNA binding determinants and can be activated to suppress tumor growth.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1078-8956
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1143-6
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Structure-based rescue of common tumor-derived p53 mutants.
pubmed:affiliation
Department of Molecular Oncology, Wistar Institute, Philadelphia, Pennsylvania 19104-4268, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't