Abstract P10: p44, the Amino-terminal Lacking Isoform of p53, is Dispensable for Tumor Suppression but Regulates Male Fertility

Abstract p53 is the most studied tumor-suppressor, by virtue of its functional inactivation in most human cancers. One aspect that has not received sufficient attention is the function of the various forms of p53, such as p47, that lacks the amino-terminal transactivation domain. Hence, the goal of this work has been to systematically characterize p47, which was found to retain the ability to selective transactivate apoptotic target gene activation (and thus the ability to induce apoptosis), but lacks the ability to induce the expression of genes involved in cell cycle arrest. Consistently, patients with tumors that have p53 mutations that lead to p47 expression have a better prognosis. We have uncovered the mechanistic basis of the selective transcriptional activity of p47, which is associated with selective co-factor binding. In addition, we have generated mice that express only p47 (without p53), and show that they are susceptible to spontaneous tumors, like human patients who have germ-line mutations that lead to only p47 expression. Thus, p47 appears to be a null allele in mice with respect to tumor formation, and is incapable of inducing selective target gene activation nor apoptosis, highlighting species-specific differences in its functionality. Further characterization of these mice will be reported. Citation Format: RH Chia, Beng Hooi Phang, Fanny Xueting Teo, Hannah Lau, Kanaga Sabapathy. p44, the Amino-terminal Lacking Isoform of p53, is Dispensable for Tumor Suppression but Regulates Male Fertility abstract. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84 (8Suppl): Abstract nr P10.