{"corpus_id":269702128,"paper_sha":"5bd96e13e27c38eb5317d4c962f4cba91bfc04dc","doi":"10.1016/j.ccell.2024.04.009","arxiv_id":null,"pmid":38729160,"pmcid":"PMC11190820","mag_id":null,"dblp_id":null,"acl_id":null,"title":"Understanding the complexity of p53 in a new era of tumor suppression.","year":2024,"publication_date":"2024-05-01","venue":"Cancer Cell","journal":{"name":"Cancer cell","pages":null,"volume":null},"journal_issn":null,"journal_title":null,"publication_types":["Review","JournalArticle"],"pubmed_pub_types":["Journal Article","Review"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":321,"citation_count":313,"influential_citation_count":6,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Tumor Suppressor Protein p53","mj":true,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D016159"},{"d":"Neoplasms","mj":true,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D009369"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Ferroptosis","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D000079403"},{"d":"Signal Transduction","mj":false,"ui":"D015398"},{"d":"Apoptosis","mj":false,"ui":"D017209"},{"d":"Protein Processing, Post-Translational","mj":false,"ui":"D011499"}],"chemicals":[{"n":"Tumor Suppressor Protein p53","ui":"D016159","reg":"0"},{"n":"TP53 protein, human","ui":"C495901","reg":"0"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"p53 was discovered 45 years ago as an SV40 large T antigen binding protein, coded by the most frequently mutated TP53 gene in human cancers. As a transcription factor, p53 is tightly regulated by a rich network of post-translational modifications to execute its diverse functions in tumor suppression. Although early studies established p53-mediated cell-cycle arrest, apoptosis, and senescence as the classic barriers in cancer development, a growing number of new functions of p53 have been discovered and the scope of p53-mediated anti-tumor activity is largely expanded. Here, we review the complexity of different layers of p53 regulation, and the recent advance of the p53 pathway in metabolism, ferroptosis, immunity, and others that contribute to tumor suppression. We also discuss the challenge regarding how to activate p53 function specifically effective in inhibiting tumor growth without harming normal homeostasis for cancer therapy.","claims":[{"public_id":"cl_176098c3d689096e84ebeeef411a8737","status":"active","text":"Recent advances have expanded the scope of p53-mediated anti-tumor activity beyond the classic barriers of cell-cycle arrest, apoptosis, and senescence.","confidence":0.94,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_176098c3d689096e84ebeeef411a8737"},{"public_id":"cl_161a1172e49fca8c3b0a73b79c4e142a","status":"active","text":"Recent progress links the p53 pathway to metabolism, ferroptosis, and immunity in tumor suppression.","confidence":0.9,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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