Abstract 258: RUNDC1 is required for p53-mediated tumor suppression

The tumor suppressor p53 is a transcription factor whose downstream target genes are involved in the regulation of the cell cycle and apoptosis, thus leading to tumor suppression. In many cancers, wild-type p53 activity is inhibited. Small molecule inhibitors of MDM2 (a negative regulator of p53), like Nutlin-3a which activates p53 by binding to MDM2, induce tumor suppression. Although p53-dependent tumor suppression is well studied, crucial factors required for the efficacy of p53-activating agents remain unknown. Toward this goal, we conducted a human whole-genome lentiviral shRNA screening in wild-type p53 carrying cells treated with Nutlin-3a. We identified RUNDC1 (Run domain containing 1) as one of crucial factors that were required for Nutlin-3a-mediated inhibition of colony formation in a p53-dependent manner. RUNDC1 is a poorly characterized protein, and its role in cancer is still unknown. Here, we demonstrated that downregulation of RUNDC1 attenuated p53-mediated cell cycle arrest. As a mechanism, RUNDC1 bound to p53 and enhanced p53’s binding to the p53-responsive elements in the promoter regions of p53 target genes. Our study, for the first time, reveals the biological function of RUNDC1, and its functional association with p53, suggesting the possibility that RUNDC1 contributes to p53-mediated tumor suppression. Citation Format: Atul Ranjan, Elizabeth Thoenen, Mrinalini Bhosale, Dipesh Thapa, Alejandro Parrales, Tomoo Iwakuma. RUNDC1 is required for p53-mediated tumor suppression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 258.