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Beschreibung

Nuclear receptor subfamily 4 group A member 1 (UniProt: P22736, also known as Early response protein NAK1, Nuclear hormone receptor NUR/77, Nur77, Orphan nuclear receptor HMR, Orphan nuclear receptor TR3, ST-59, Testicular receptor 3) is encoded by the NR4A1 (also known as GFRP1, HMR, NAK1) gene (Gene ID: 3164) in human. Nur77 is an orphan nuclear receptor that may act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. It is shown to be expressed in fetal muscle and in adult liver, brain, and thyroid and is reported to be induced by growth stimulating agents. It binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3'. Its DNA binding region is localized to amino acids 264-339. It contains two zinc finger domains (aa 267-287 and 303-327). Nur77 is shown to heterodimerize with retinoid X receptor alpha and is actively transported from the nucleus to the mitochondria in cells undergoing apoptosis. It binds to Bcl-2 and triggers a conformational change that exposes the pro-apoptotic BH3 domain. This converts Bcl-2 from an anti-apoptotic to a pro-apoptotic factor. In several cancers the nuclear-mitochondrial translocation of Nur77/TR3 is defective, which prevents apoptosis. Three isoforms of Nur77 have been described that are produced by alternative splicing. It is acetylated by p300/CBP that increases its stability. It can also undergo phosphorylation at Serine 351 by RPS6KA1 and RPS6KA3 in response to mitogenic or stress stimuli.