Project Summary/Abstract The p53 protein is an important tumor suppressor and a frequent target of mutations in human cancer. MDM2 and MDMX are important negative regulators of p53 by acting as ubiquitin E3 ligase to promote p53 degradation, and by binding and inhibiting p53 transcriptional functions. Missense mutation of p53 occurs in over 50% of human tumors. Accumulation of mutant p53 protein in tumor cells due to deficiency in MDM2- mediated ubiquitination leads to gain of function that promotes tumor progression. In human tumors with wild type p53, MDM2 and MDMX play important roles in functionally inactivating p53. Amplification of MDM2 and MDMX are associated with adverse hyperprogressive response to anti-PDL1 cancer immunotherapy in a subset of patients. A p53 Workshop is held every two years to bring together the p53 field in order to report on the latest research and to facilitate collaboration. The first p53 Workshop was held in 1983 in the United Kingdom. The scientific need for the MDM2 Workshop arises from the central role of the p53/MDM2/MDMX pathway in the initiation and progression of human cancer, and the promise that p53- MDM2/X interaction holds for development of novel therapies. The complexity of the p53 pathway, expansion of the scientific community studying p53/MDM2/MDMX, and the need for collaborative multi- disciplinary approach has further made it necessary to have MDM2 Workshops. In 2001, the first complementing MDM2 Workshop was held in alternating years with the p53 conference. The MDM2 Workshop has since been held every two years, alternating between Europe and the United States. While both p53 and MDM2 Workshops started as small self-organized gatherings of researchers in the field, they have become important platforms of scientific exchange for long-term and new investigators of p53 pathway. The 9th International MDM2 Workshop will be held on November 4-7th, 2018 at the Don CeSar Hotel in the city of St. Pete Beach, Florida. The meeting is being co-organized by investigators from the Moffitt Cancer Center in Tampa, Florida (Jiandong Chen, Elsa Flores, John Cleveland). We are applying for the R13 funding to support this important international meeting in the p53 field, which will continue to energize research and promote scientific progress on a prominent cancer pathway.