Matches in SemOpenAlex for { <https://semopenalex.org/work/W20512754> ?p ?o ?g. }
Showing items 1 to 63 of
63
with 100 items per page.
- W20512754 endingPage "11" @default.
- W20512754 startingPage "9" @default.
- W20512754 abstract "Mechanisms to protect organisms from the consequences of DNA damage include the tumor suppressor p53 pathway. p53 protein binds specifically to a DNA consensus sequence to induce growth inhibitory genes or nonspecifically to damaged sites leading to DNA repair or apoptosis. While p53 protein is susceptible to post-translational modifications and binding to other proteins, few of the modifications or associations have been demonstrated in the context of the cell. We used a novel, sensitive DNA binding assay to examine p53 proteins in lysates prepared from cells responding to DNA damage. Non-transformed progenitor keratinocytes exhibited rapid and sustained induction of activated p53 protein binding to the consensus sequence, correlated with sustained induction of a downstream target gene, the cyclin-dependent kinase inhibitor p21. Binding to a mismatched DNA probe was transient and correlated with total p53 protein in the lysate, suggesting that most or all of the endogenous p53 proteins induced after damage were capable of mismatched DNA binding. Squamous cell carcinoma (SCC) derivates showed defects in induction p53 protein after DNA damage and disproportional losses in DNA binding, compared to total p53 protein steady state levels, along with increased NDN2/p53 association. Maximum induction of endogenous p53 protein binding to the mismatched probe correlated with transcription-independent induction of apoptosis. We suggest a model in which activated forms of p53 carry out transcription-dependent functions in growth arrest and DNA repair which may vary by cell type, while most or all wild type forms of p53 are capable of binding to damaged DNA. p53 protein loss of binding to damaged DNA causes failure of cells to trigger apoptosis and may lead to resistance to chemotherapy. Implications for new directions in therapeutics include functional molecular profiling of individual patient tumors for p53 DNA binding to predict treatment response better than mutational analysis alone and targeted activation of p53 DNA damage binding in tumor cells for increasing their sensitivity to chemotherapy." @default.
- W20512754 created "2016-06-24" @default.
- W20512754 creator A5071117583 @default.
- W20512754 creator A5088490223 @default.
- W20512754 date "2000-01-01" @default.
- W20512754 modified "2023-10-18" @default.
- W20512754 title "P53 regulation and function in normal cells and tumors." @default.
- W20512754 cites W1586543322 @default.
- W20512754 cites W1809276377 @default.
- W20512754 cites W1971966311 @default.
- W20512754 cites W1978518304 @default.
- W20512754 cites W2032205501 @default.
- W20512754 cites W2114067749 @default.
- W20512754 cites W2341209396 @default.
- W20512754 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11188940" @default.
- W20512754 hasPublicationYear "2000" @default.
- W20512754 type Work @default.
- W20512754 sameAs 20512754 @default.
- W20512754 citedByCount "5" @default.
- W20512754 countsByYear W205127542016 @default.
- W20512754 countsByYear W205127542017 @default.
- W20512754 countsByYear W205127542022 @default.
- W20512754 crossrefType "journal-article" @default.
- W20512754 hasAuthorship W20512754A5071117583 @default.
- W20512754 hasAuthorship W20512754A5088490223 @default.
- W20512754 hasConcept C104317684 @default.
- W20512754 hasConcept C134935766 @default.
- W20512754 hasConcept C143425029 @default.
- W20512754 hasConcept C153911025 @default.
- W20512754 hasConcept C552990157 @default.
- W20512754 hasConcept C55493867 @default.
- W20512754 hasConcept C86339819 @default.
- W20512754 hasConcept C86803240 @default.
- W20512754 hasConcept C95444343 @default.
- W20512754 hasConceptScore W20512754C104317684 @default.
- W20512754 hasConceptScore W20512754C134935766 @default.
- W20512754 hasConceptScore W20512754C143425029 @default.
- W20512754 hasConceptScore W20512754C153911025 @default.
- W20512754 hasConceptScore W20512754C552990157 @default.
- W20512754 hasConceptScore W20512754C55493867 @default.
- W20512754 hasConceptScore W20512754C86339819 @default.
- W20512754 hasConceptScore W20512754C86803240 @default.
- W20512754 hasConceptScore W20512754C95444343 @default.
- W20512754 hasLocation W205127541 @default.
- W20512754 hasOpenAccess W20512754 @default.
- W20512754 hasPrimaryLocation W205127541 @default.
- W20512754 hasRelatedWork W1485654493 @default.
- W20512754 hasRelatedWork W1862183444 @default.
- W20512754 hasRelatedWork W1949617809 @default.
- W20512754 hasRelatedWork W1983626749 @default.
- W20512754 hasRelatedWork W1989210919 @default.
- W20512754 hasRelatedWork W2022208109 @default.
- W20512754 hasRelatedWork W2063438416 @default.
- W20512754 hasRelatedWork W2317146774 @default.
- W20512754 hasRelatedWork W2384475959 @default.
- W20512754 hasRelatedWork W2974909977 @default.
- W20512754 hasVolume "60 Suppl 2" @default.
- W20512754 isParatext "false" @default.
- W20512754 isRetracted "false" @default.
- W20512754 magId "20512754" @default.
- W20512754 workType "article" @default.