Characterization of the Golgi scaffold protein PAQR3, and its role in tumor suppression and metabolic pathway compartmentalization

The Golgi apparatus is critical in the compartmentalization of signaling cascades originating from the cytoplasmic membrane and various organelles. Scaffold proteins, such as progestin and adipoQ receptor (PAQR)3, specifically regulate this process, and have recently been identified in the Golgi apparatus. PAQR3 belongs to the PAQR family, and was recently described as a tumor suppressor. Accumulating evidence demonstrates PAQR3 is downregulated in different cancers to suppress its inhibitory effects on malignant potential. PAQR3 functions biologically through the pathological regulation of altered signaling pathways. Significant cell proliferation networks, including Ras proto-oncogene (Ras)/mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), insulin, and vascular endothelial growth factor, are closely controlled by PAQR3 for physiologically relevant effects. Meanwhile, genetic/epigenetic susceptibility and environmental factors, may have functions in the downregulation of PAQR3 in human cancers. This study aimed to assess the subcellular localization of PAQR3 and determine its topological features and functional domains, summarizing its effects on cell signaling compartmentalization. The pathophysiological functions of PAQR3 in cancer pathogenesis, metabolic diseases, and developmental ailments were also highlighted.