GPS2
Description
The GPS2 (G protein pathway suppressor 2) is a protein-coding gene located on chromosome 17.
GPS2 may refer to:
GPS2 is a key regulator of inflammation, lipid metabolism, and mitochondrial homeostasis. It acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, thereby preventing 'Lys-63'-linked ubiquitination. In the nucleus, GPS2 can act as both a corepressor and a coactivator of transcription, depending on the context. As a coactivator in adipocytes, it promotes the recruitment of PPARG to promoters, leading to stabilization of KDM4A and subsequent histone H3 'Lys-9' (H3K9) demethylation. GPS2 also promotes cholesterol efflux as a coactivator. It regulates B-cell development by inhibiting UBE2N/Ubc13, thereby restricting the activation of Toll-like receptors (TLRs) and B-cell antigen receptors (BCRs) signaling pathways. In response to mitochondrial stress, GPS2 relocates from the mitochondria to the nucleus and promotes the expression of nuclear-encoded mitochondrial genes. It acts as a corepressor in the N-Cor repressor complex, repressing active PPARG. This corepressor function plays an anti-inflammatory role in macrophages and is essential for insulin sensitivity. GPS2 also has an anti-inflammatory role during the hepatic acute phase response by interacting with sumoylated NR1H2 and NR5A2 proteins. In the cytosol, GPS2 regulates insulin signaling and pro-inflammatory pathways. It acts as a negative regulator of inflammation by inhibiting the pro-inflammatory TNF-alpha pathway, repressing UBE2N/Ubc13 activity. In adipocytes, it restricts the activation of insulin signaling by inhibiting UBE2N/Ubc13-mediated ubiquitination of AKT. GPS2 can also suppress G-protein- and mitogen-activated protein kinase-mediated signal transduction. It acts as a tumor suppressor in liposarcoma.
GPS2 is also known as AMF-1.
