Abstract 5644: The impact of ATF3, JDP2, FOXR2, NAA10, FOXL2, DDX20, and p14ARF on the transactivation of p53

Abstract Cancer stands as a formidable health challenge in the 21st century, evoking widespread fear. Presently, the mortality rate associated with cancer in humans ranges from approximately 11% to 25%. Numerous nuclear and cytoplasmic proteins have demonstrated interactions with p53, influencing both its activity and abundance. In our prior, unpublished findings, we established that JDP2 interacts with p53, modulating its activity. Consequently, in the present investigation, we broaden our exploration to identify novel proteins capable of regulating p53 transactivation. First, we found a synergistic effect of ATF3 and JDP2 on p53 transactivation. Moreover, deSUMOylation of ATF3 and dephosphorylation of JDP2 further enhance p53 transactivation. Secondly, FOXR2 (an epigenetically regulated pan-cancer oncogene) and NAA10 (an acetyltransferase) also remarkably increase p53 transactivation in H1299 (p53 null) cells. Thirdly, in addition to MDM2 and MDM4 (MDMX) as p53 negative regulators, we further found that FOXL2 (a transcription factor in steroidogenesis regulation), DDX20 (a transcription factor for embryonic development and ovarian function), and p14ARF (for cell cycle regulation) significantly down-regulate p53 transactivation. Taken together, our preliminary results demonstrate that several transcription factors regulate p53 transactivation and possible p53 stability and/or degradation. This data is presented to substantiate the idea that numerous newly discovered proteins may engage with p53 and control its transactivation. Citation Format: William H. Yang, Wei-Hsiung Yang. The impact of ATF3, JDP2, FOXR2, NAA10, FOXL2, DDX20, and p14ARF on the transactivation of p53 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5644.