Nfatc2ip-KO Mouse

Nfatc2ip, also known as NIP45, is an evolutionarily conserved protein with tandem SUMO-like domains. It is crucial for SUMO-dependent genome integrity. It acts in interphase, associates with nascent DNA, and is involved in post-replicative resolution of replication or recombination intermediates. It interacts with the SMC5/6 complex and UBC9 (SUMO E2) via its SUMO-like domains, and is part of pathways related to genome duplication, repair, and cell proliferation [1,3].

Cells lacking Nfatc2ip are viable but hypersensitive to SUMO E1 inhibition, showing mitotic chromosome bridges and micronuclei, suggesting its key role in maintaining genomic integrity [1]. In breast cancer, TRPV6 activates NFATC2 by increasing Nfatc2ip phosphorylation at Ser204, promoting breast cancer metastasis [2]. In rainbow trout, miR-301b-5p and Nfatc2ip regulate inflammatory responses in the liver under high-temperature stress [5]. In myocardial hypertrophy, miR-31-5p targets Nfatc2ip to inhibit the process [4].

In summary, Nfatc2ip is essential for SUMO-dependent genome integrity. Its study through loss-of-function models has revealed its roles in various biological processes and disease conditions such as cancer metastasis, inflammatory responses, and myocardial hypertrophy. Understanding Nfatc2ip provides insights into the underlying mechanisms of these biological events and potential therapeutic targets.