TP53 is a tumor suppressor gene that is the most frequently mutated gene in human cancer. It’s protein product, p53, is a transcription factor that is activated in response to genotoxic and cytotoxic stress to transcriptionally coordinate over 3000 genes involved in cell cycle arrest, DNA repair, apoptosis, metabolism, and autophagy. Since p53 has so many diverse roles in protecting the integrity of the genome and maintaining homeostasis, several mechanisms exist to regulate and fine-tune p53 functions. Post-translational modifications influence p53 activity by affecting its stability, localization, and protein-protein interactions. Using mass spectrometry, I have identified citrullination as a novel post-translational modification on p53, and peptidyl arginine de-iminase type 4 (PADI4) has been identified as the enzyme responsible for the nonreversible conversion of arginine to citrulline on p53. We found that PADI4 is a p53 target gene, that it fails to be transactivated by tumor-associated p53 hypomorphic variants studied in our lab, and that overexpression of PADI4 results in a tumor suppressive phenotype both in vitro and in vivo. We performed ChIP-seq on PADI4-induced and p53-stabilized cells and found that PADI4 and p53 colocalize at the promoter region of a small subset of p53 target genes that regulate metabolism and autophagy, including PRKAB1(AMPK), and PTEN. A regulatory network analysis of our data confirmed that a large majority of these target genes are also co-regulated by the stress-induced activating transcription factor 3 (ATF3). Using a genome browser, I have identified ATF3 binding motifs near the promotors of PRKAB1, and PTEN. My data support the hypothesis that PADI4 binds to p53 and citrullinates it, resulting in enhanced binding to promoter regions near ATF3 binding sites, potentially through altered protein-protein interactions with ATF3. This work has the potential to uncover new pathways that regulate tumor suppression by p53.