PRL-3 activates NF-κB signaling pathway by interacting with RAP1

► PRL-3 interacts with telomere-related protein RAP1. ► PRL-3 promotes cytosolic localization of RAP1. ► RAP1 contributes to PRL-3-regulated gene expression and phosphorylation of p65. ► PRL-3 enhances RAP1 expression in a p65-dependent manner.