FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2146223593> ?p ?o ?g. }

• W2146223593 endingPage "265" @default.
• W2146223593 startingPage "249" @default.
• W2146223593 abstract "The tumor suppressor protein p53 is mutated in more than 50% of invasive cancers. About 30% of the mutations are found in six major “hot spot” codons located in its DNA binding core domain. To gain structural insight into the deleterious effects of such mutations and their rescue by suppressor mutations, we determined the crystal structures of the p53 core domain incorporating the hot spot mutation R249S, the core domain incorporating R249S and a second-site suppressor mutation H168R (referred to as the double mutant R249S/H168R) and its sequence-specific complex with DNA and of the triple mutant R249S/H168R/T123A. The structural studies were accompanied by transactivation and apoptosis experiments. The crystal structures show that the region at the vicinity of the mutation site in the R249S mutant displays a range of conformations [wild-type (wt) and several mutant-type conformations] due to the loss of stabilizing interactions mediated by R249 in the wt protein. As a consequence, the protein surface that is critical to the formation of functional p53–DNA complexes, through protein–protein and protein–DNA interactions, is largely distorted in the mutant conformations, thus explaining the protein's “loss of function” as a transcription factor. The structure of this region is restored in both R249S/H168R and R249S/H168R/T123A and is further stabilized in the complex of R249S/H168R with DNA. Our functional data show that the introduction of H168R as a second-site suppressor mutation partially restores the transactivation capacity of the protein and that this effect is further amplified by the addition of a third-site mutation T123A. These findings together with previously reported data on wt and mutant p53 provide a structural framework for understanding p53 dysfunction as a result of oncogenic mutations and its rescue by suppressor mutations and for a potential drug design aimed at restoring wt activity to aberrant p53 proteins." @default.
• W2146223593 created "2016-06-24" @default.
• W2146223593 creator A5001638768 @default.
• W2146223593 creator A5001691853 @default.
• W2146223593 creator A5002972268 @default.
• W2146223593 creator A5022394866 @default.
• W2146223593 creator A5048307240 @default.
• W2146223593 creator A5058203625 @default.
• W2146223593 creator A5068783230 @default.
• W2146223593 creator A5083554694 @default.
• W2146223593 creator A5083967477 @default.
• W2146223593 creator A5086773368 @default.
• W2146223593 date "2009-01-01" @default.
• W2146223593 modified "2023-10-17" @default.
• W2146223593 title "Structural Basis of Restoring Sequence-Specific DNA Binding and Transactivation to Mutant p53 by Suppressor Mutations" @default.
• W2146223593 cites W132441100 @default.
• W2146223593 cites W140845169 @default.
• W2146223593 cites W1640635403 @default.
• W2146223593 cites W1650797637 @default.
• W2146223593 cites W1973368924 @default.
• W2146223593 cites W1974477141 @default.
• W2146223593 cites W1986076152 @default.
• W2146223593 cites W1991494214 @default.
• W2146223593 cites W1995017064 @default.
• W2146223593 cites W1999392340 @default.
• W2146223593 cites W2001641653 @default.
• W2146223593 cites W2008257691 @default.
• W2146223593 cites W2009871049 @default.
• W2146223593 cites W2015519364 @default.
• W2146223593 cites W2016455125 @default.
• W2146223593 cites W2018586811 @default.
• W2146223593 cites W2025977492 @default.
• W2146223593 cites W2029230946 @default.
• W2146223593 cites W2034227568 @default.
• W2146223593 cites W2042075518 @default.
• W2146223593 cites W2043730018 @default.
• W2146223593 cites W2047004797 @default.
• W2146223593 cites W2047596219 @default.
• W2146223593 cites W2049137769 @default.
• W2146223593 cites W2049499385 @default.
• W2146223593 cites W2062202414 @default.
• W2146223593 cites W2063669247 @default.
• W2146223593 cites W2072052957 @default.
• W2146223593 cites W2073576377 @default.
• W2146223593 cites W2074222004 @default.
• W2146223593 cites W2079328211 @default.
• W2146223593 cites W2080125477 @default.
• W2146223593 cites W2081288740 @default.
• W2146223593 cites W2082103873 @default.
• W2146223593 cites W2083627679 @default.
• W2146223593 cites W2090025028 @default.
• W2146223593 cites W2096276671 @default.
• W2146223593 cites W2099459640 @default.
• W2146223593 cites W2118455767 @default.
• W2146223593 cites W2118738597 @default.
• W2146223593 cites W2119489910 @default.
• W2146223593 cites W2128080369 @default.
• W2146223593 cites W2144081223 @default.
• W2146223593 cites W2149573413 @default.
• W2146223593 cites W2150710841 @default.
• W2146223593 cites W2152023928 @default.
• W2146223593 cites W2168497623 @default.
• W2146223593 cites W2171407623 @default.
• W2146223593 cites W2312641146 @default.
• W2146223593 cites W4230595181 @default.
• W2146223593 doi "https://doi.org/10.1016/j.jmb.2008.10.063" @default.
• W2146223593 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18996393" @default.
• W2146223593 hasPublicationYear "2009" @default.
• W2146223593 type Work @default.
• W2146223593 sameAs 2146223593 @default.
• W2146223593 citedByCount "48" @default.
• W2146223593 countsByYear W21462235932012 @default.
• W2146223593 countsByYear W21462235932013 @default.
• W2146223593 countsByYear W21462235932014 @default.
• W2146223593 countsByYear W21462235932015 @default.
• W2146223593 countsByYear W21462235932016 @default.
• W2146223593 countsByYear W21462235932017 @default.
• W2146223593 countsByYear W21462235932018 @default.
• W2146223593 countsByYear W21462235932019 @default.
• W2146223593 countsByYear W21462235932020 @default.
• W2146223593 countsByYear W21462235932021 @default.
• W2146223593 countsByYear W21462235932022 @default.
• W2146223593 countsByYear W21462235932023 @default.
• W2146223593 crossrefType "journal-article" @default.
• W2146223593 hasAuthorship W2146223593A5001638768 @default.
• W2146223593 hasAuthorship W2146223593A5001691853 @default.
• W2146223593 hasAuthorship W2146223593A5002972268 @default.
• W2146223593 hasAuthorship W2146223593A5022394866 @default.
• W2146223593 hasAuthorship W2146223593A5048307240 @default.
• W2146223593 hasAuthorship W2146223593A5058203625 @default.
• W2146223593 hasAuthorship W2146223593A5068783230 @default.
• W2146223593 hasAuthorship W2146223593A5083554694 @default.
• W2146223593 hasAuthorship W2146223593A5083967477 @default.
• W2146223593 hasAuthorship W2146223593A5086773368 @default.
• W2146223593 hasConcept C104317684 @default.
• W2146223593 hasConcept C1292079 @default.
• W2146223593 hasConcept C143065580 @default.
• W2146223593 hasConcept C153911025 @default.

• next