Functional Changes Associated With the Subcellular Localization of the Nuclear Receptor NR4A1.

Abstract

Nuclear receptor subfamily 4 group A member 1 (NR4A1), which is also known as nuclear receptor 77 (NUR77), NGFI-B, or testicular receptor 3 (TR3), is a member of the NR4A subfamily of the nuclear receptor superfamily. NR4A1 has both nuclear localization and nuclear export signals, and NR4A1 is present in the cytoplasm as well as the nucleus. NR4A1 alters its subcellular localization through phosphorylation or SUMOylation. In the nucleus, NR4A1 plays an important role in regulating gene expression by directly binding to genomic DNA or indirectly influencing other transcription factors. In the cytoplasm, NR4A1 affects the stabilization of β-catenin, which is involved in various tumorigenesis. Furthermore, NR4A1 is involved in LPS-induced inflammasome activation. In mitochondria and endoplasmic reticulum, NR4A1 plays an important role in the induction of autophagy and apoptosis. In this review, we focused on the current knowledge of subcellular localization and molecular function of NR4A1.