Paper Title
CRITICAL ROLE OF NOVEL O-GLCNACYLATION OF NF-KB IN PANCREATIC CANCER

Abstract
NF-kB is an inflammatory protein that contributes to the low rate of survivalobserved in pancreatic cancer patients. The activation of NF-kB causes high expression of proteinsthat drive and sustain pancreatic cancer growth. Thus, it is important to understand how NF-kB is regulated to help with the diagnosis and treatment of pancreatic cancer. In this study, wediscovered that the typical NF-kB subunit p65 is modified by O-GlcNAc at serines (S)550 and S551.To characterize the role of O-GlcNAcylated p65 at S550 and S551, we overexpressed p65 serine-to-alanine(S-A) mutants, such as S550A, S551A, and S550A/S551A, in pancreatic cancer cells. Using thismodel, we show that the p65 mutants reduce NF-kB transcriptional activity, nuclear translocation,p65 phosphorylation, and target gene expression. We also observed that the p65 mutants blockedpancreatic cancer cell growth and migration. This suggests the contribution of p65 O-GlcNAcylationat S550 and S551 to pancreatic cancer phenotypes. Taken together, our study uncovers a novelaspect of NF-kB regulation, which could aid future therapeutic development by targeting O-GlcNActransferase (OGT) in pancreatic cancer.