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Structural studies have revealed that iASPP employs distinct molecular surfaces, including regions from its ankyrin repeats and SH3 domain, to displace critical p53 loops required for optimal DNA binding, suggesting a mechanism amenable to targeted therapeutic interference."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in restraining p53, dysregulated iASPP contributes to oncogenesis by promoting tumor cell proliferation, invasion, and chemoresistance across multiple cancer types. Alterations in PPP1R13L expression—whether by gene polymorphisms, transcriptional deregulation, or post‐transcriptional modulation via non‐coding RNAs such as H19, UCA1, XIST, and TP73‐AS1—have been implicated in the progression of acute leukemia, glioma, lung, ovarian, and hepatocellular carcinomas. Elevated iASPP not only suppresses apoptosis and skews cell-cycle progression but also indirectly modulates other pathways such as oxidative stress responses via Nrf2 regulation, thereby reinforcing resistance to conventional therapies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its well‐established oncogenic functions, iASPP plays a multifaceted role in normal tissue homeostasis. By influencing key differentiation pathways in epithelial and hematopoietic lineages, it helps maintain cellular integrity under physiological conditions while its aberrant overexpression correlates with aggressive disease and therapy resistance in cancers such as cervical and prostate carcinoma. These insights, together with detailed structural delineation of its interaction interfaces, underscore PPP1R13L’s potential as both a prognostic biomarker and a target for precision therapeutic strategies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Daniele Bergamaschi, Yardena Samuels, Alexandra Sullivan, et al. 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