Nur77 Activators

Nur77, also known as NR4A1, belongs to the nuclear receptor superfamily and plays a crucial role in regulating various cellular processes, including apoptosis, inflammation, and metabolism. The identified chemicals act as activators of Nur77 through distinct pathways, demonstrating the protein's versatility in responding to different cellular signals. Forskolin stimulates Nur77 activation through cAMP-dependent pathways, indicating the involvement of CREB-mediated transcriptional regulation. PMA induces Nur77 phosphorylation via the PKC-ERK/MAPK cascade, highlighting the intricate interplay between protein kinase activities. A23187 triggers Nur77 activation by elevating intracellular calcium levels, demonstrating the significance of calcium-dependent signaling in Nur77 regulation.

Dibutyryl cAMP and GW0742 exemplify the crosstalk between Nur77 and nuclear receptors, with cAMP/PKA and PPARβ/δ pathways influencing Nur77 expression, respectively. The potassium channel enhancer 4-aminopyridine showcases how ion channels can modulate Nur77 through calcium-dependent pathways. SB202190 and H89 underscore the role of kinases in Nur77 activation, with p38 MAPK and PKA inhibitors attenuating Nur77 phosphorylation. Thapsigargin-induced ER stress and Dimethyl Fumarate activation of Nrf2 demonstrate the integration of Nur77 into cellular stress response pathways. Calyculin A and A769662 highlight the importance of phosphatase inhibition and AMPK activation, respectively, in Nur77 regulation.