A SUMO-interacting motif in the guanine nucleotide exchange factor EPAC1 is required for subcellular targeting and function.

ABSTRACT: Exchange protein directly activated by cAMP (EPAC1), a multifunctional intracellular cAMP receptor, dynamically localizes to various cellular loci, engaging with diverse molecular partners to maintain cellular homeostasis. The study investigates the role of the SUMO-interacting motif (SIM) in the subcellular targeting and cellular functions of EPAC1. It reveals that the SIM is a critical structural element for EPAC1's association with RanBP2/nucleoporin 358, a nucleoporin of the cytoplasmic filament component of the nuclear pore complex. Mutational disruption of EPAC1 SIM interferes with EPAC1's ability to activate its canonical effectors, small GTPases, Rap1 and Rap2, and noncanonical functions, such as the formation of nuclear condensates and cellular SUMOylation. Because SIM is also dir

SUBMITTER: Yang W 

PROVIDER: S-EPMC12226364 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature