{"@type": "dcat:Dataset", "accessLevel": "public", "bureauCode": ["009:25"], "contactPoint": {"@type": "vcard:Contact", "fn": "NIH", "hasEmail": "mailto:info@nih.gov"}, "description": "Background\n          The p53 protein is activated by genotoxic stress, oncogene expression and during senescence, p53 transcriptionally activates genes involved in growth arrest and apoptosis. p53 activation is regulated by post-translational modification, including phosphorylation of the N-terminal transactivation domain. Here, we have examined how Glycogen Synthase Kinase (GSK3), a protein kinase involved in tumorigenesis, differentiation and apoptosis, phosphorylates and regulates p53.\n        \n        \n          Results\n          The 2 isoforms of GSK3, GSK3\u03b1 and GSK3\u03b2, phosphorylate the sequence Ser-X-X-X-Ser(P) when the C-terminal serine residue is already phosphorylated. Several p53 kinases were examined for their ability to create GSK3 phosphorylation sites on the p53 protein. Our results demonstrate that phosphorylation of serine 37 of p53 by DNA-PK creates a site for GSK3\u03b2 phosphorylation at serine 33 in vitro. GSK3\u03b1 did not phosphorylate p53 under any condition. GSK3\u03b2 increased the transcriptional activity of the p53 protein in vivo. Mutation of either serine 33 or serine 37 of p53 to alanine blocked the ability of GSK3\u03b2 to regulate p53 transcriptional activity. GSK3\u03b2 is therefore able to regulate p53 function in vivo. p53's transcriptional activity is commonly increased by DNA damage. However, GSK3\u03b2 kinase activity was inhibited in response to DNA damage, suggesting that GSK3\u03b2 regulation of p53 is not involved in the p53-DNA damage response.\n        \n        \n          Conclusions\n          GSK3\u03b2 can regulate p53's transcriptional activity by phosphorylating serine 33. However, GSK3\u03b2 does not appear to be part of the p53-DNA damage response pathway. Instead, GSK3\u03b2 may provide the link between p53 and non-DNA damage mechanisms for p53 activation.", "distribution": [{"@type": "dcat:Distribution", "description": "Visit the original government dataset for complete information, documentation, and data access.", "downloadURL": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC35361/", "mediaType": "text/html", "title": "Official Government Data Source"}], "identifier": "https://healthdata.gov/api/views/rrtb-jx2r", "issued": "2025-07-14", "keyword": ["dna-pk", "gsk3-beta", "nih", "p53-phosphorylation", "tumor-suppressor"], "landingPage": "https://healthdata.gov/d/rrtb-jx2r", "modified": "2025-09-06", "programCode": ["009:033"], "publisher": {"@type": "org:Organization", "name": "National Institutes of Health"}, "theme": ["NIH"], "title": "Glycogen synthase kinase3 beta phosphorylates serine 33 of p53 and activates p53's transcriptional activity"}