Nuclear factor of activated T cells 2 interacting protein (NFATC2IP)

Nuclear factor of activated T cells 2 interacting protein (NFATC2IP) is a conserved, chromatin-associated protein that interacts directly with the SUMOylation machinery, particularly the SMC5/6 complex and the E2 enzyme UBC9 via its SUMO-like domains. NFATC2IP plays a crucial role in maintaining genome integrity and cell survival, especially under conditions where SUMOylation is inhibited, by preventing chromosomal aberrations such as micronuclei and chromosome bridges and by promoting the SUMOylation of chromatin-associated proteins. In T-helper 2 lymphocytes, NFATC2IP modulates transcription of a subset of cytokine genes (including IL3, IL4, IL5, IL13), partly by recruiting coactivators and facilitating histone modifications (notably histone H4 Arg-3 methylation and acetylation at the IL4 locus). Although not itself a classical therapeutic target such as a receptor or enzyme, it is essential for cellular response to DNA damage and for proper chromosomal segregation, and its activity is required for resistance to SUMOylation inhibitors in cell-based studies[1][2][3][4][5].

Other names

Nuclear factor of activated T-cells 2 interacting proteinNIP45ESC2RAD60FLJ1463945 kDa NFAT-interacting proteinnuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 2 interacting proteinD7Ertd304e

Inhibition of SUMOylation exposes NFATC2IP-dependent survival/genome maintenance pathway (TAK-981 renders cells dependent on NFATC2IP for chromosomal stability, but this is mechanistic, not therapeutic)[1]