Linked Life Data

19754415

Source:http://linkedlifedata.com/resource/pubmed/id/19754415

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
32
pubmed:dateCreated
2009-11-20
pubmed:abstractText
p53 and its related genes, p73 and p63, are members of the p53 gene family. While p53 is the most frequently mutated gene in human tumors, p73 and p63 are rarely mutated or lost in cancers. Although p53-deficient cancer cells are often less responsive to chemotherapy, they are not completely drug resistant, suggesting that other apoptotic pathways are at work. Interestingly, several studies have shown that p73, and more recently p63, are involved in cellular response to cancer therapy, while others have indicated that p63 and p73 are required for p53-induced apoptosis, delineating functional interplay between p53 family members. The latest reports in this field have established that Nutlin-3, a selective inhibitor of p53-MDM2 interaction, disrupts p73-MDM2 and enhances p73 function in p53-null cells, and that a p53-derived peptide that targets iASPP--a common negative regulator of p53 family members--can trigger cell death via a p73-dependent mechanism. It has also been shown that a small-molecule RETRA suppressed mutant p53-bearing cancers cells through a p73-dependent salvage pathway. Finally, there is increasing evidence that cleaved fragments of p53, p63 and p73 are involved in apoptosis and it remains to be determined whether or not pro-forms of the p53 family play an apoptotic role mediated by cleavage. This review will highlight research into drugs and mechanisms that activate p63 and p73, since these proteins are not mutated in cancers and as such are potential candidates for replacing p53 in p53-deficient cells. It will therefore focus on recent findings in the search for pathways and molecules capable of modulating p53 family protein activities and restoring response to cancer therapy, particularly in tumors bearing p53 mutations.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1875-533X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4328-44
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
P53 family: at the crossroads in cancer therapy.
pubmed:affiliation
UPRESS 3535, Pharmacologie et Nouveaux Traitements des Cancers (IFR 54), Institut de Cancérologie Gustave Roussy, Rue Camille Desmoulins, 94805 Villejuif Cedex, France.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't