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As the \"guardian of the genome\", it prevents the initiation and development of tumors by inducing mechanisms such as DNA repair, senescence, and apoptosis. However, these mechanisms may also influence aging. Strikingly, stability-modulating structural changes in p53 have been linked to organismal longevity in mouse models: for example, the lifespans of mice have decreased following truncation of the N- or C-terminal of p53, inhibition of Mdm2-p53 complex formation, and point mutation at residue P72. Yet, the molecular and biochemical consequences of these structural changes and their potential impact on longevity across other vertebrates remain unclear.</p><p>This thesis employs structural bioinformatics in probing a link between p53 structure and organismal longevity among vertebrates. Genotype-phenotype correlation analyses, functional enrichment, and Rosetta-based modeling are employed to predict longevity-associated residues in p53 and reveal potential structure-function dynamics of p53 regulation of longevity. These longevity-associated residues (or RPLARs) reside primarily in the DNA-binding domain. RPLARs in the human p53 ortholog may modulate its stability and tumor suppressive functions by augmenting the destabilizing effect of cancer hotspots and facilitating protein-protein interactions with partners such as Fgf1, Gps2, and Yy1. These findings highlight potential links between p53 stabilization and organismal longevity, offering insights into how p53 may modulate tumor suppression and aging processes across vertebrates.</p>"},{"label":"Group","value":["Theses & Dissertations"]},{"label":"Digital Origin","value":["born digital"]},{"label":"Discipline","value":["Molecular Biology and Biochemistry"]},{"label":"Date","value":"April 15, 2025"},{"label":"EDTF Date","value":"D:00 M:00 Y:2025"},{"label":"File Format","value":["application/pdf"]},{"label":"Digital Object Identifier (DOI)","value":"https://doi.org/10.14418/wes01.1.3058"},{"label":"Type","value":["Text"]}],"description":"Bioinformatics probing of tumor suppressor p53's structure-function dynamics in longevity 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