Linked Life Data

8875929

Source:http://linkedlifedata.com/resource/pubmed/id/8875929

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5289
pubmed:dateCreated
1996-12-6
pubmed:databankReference
pubmed:abstractText
The MDM2 oncoprotein is a cellular inhibitor of the p53 tumor suppressor in that it can bind the transactivation domain of p53 and downregulate its ability to activate transcription. In certain cancers, MDM2 amplification is a common event and contributes to the inactivation of p53. The crystal structure of the 109-residue amino-terminal domain of MDM2 bound to a 15-residue transactivation domain peptide of p53 revealed that MDM2 has a deep hydrophobic cleft on which the p53 peptide binds as an amphipathic alpha helix. The interface relies on the steric complementarity between the MDM2 cleft and the hydrophobic face of the p53 alpha helix and, in particular, on a triad of p53 amino acids-Phe19, Trp23, and Leu26-which insert deep into the MDM2 cleft. These same p53 residues are also involved in transactivation, supporting the hypothesis that MDM2 inactivates p53 by concealing its transactivation domain. The structure also suggests that the amphipathic alpha helix may be a common structural motif in the binding of a diverse family of transactivation factors to the TATA-binding protein-associated factors.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0036-8075
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
948-53
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain.
pubmed:affiliation
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. nikola@xray2.mskcc.org
pubmed:publicationType
Journal Article, Comment, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't