Complex and pleiotropic signaling pathways regulated by the secreted protein augurin

The secreted protein augurin, the product of the tumor suppressor gene Ecrg4, has been identified as a peptide hormone in the human proteome in 2007. Since then, a number of studies have been carried out to highlight its structure and processing and its potential roles in physiopathology. Although augurin has been shown to be implicated in a variety of processes, ranging from tumorigenesis, inflammation and infection to neural stem cell proliferation, hypothalamo-pituitary adrenal axis regulation and osteoblast differentiation, the molecular mechanisms of its biological effects and the signaling pathways it regulates are still poorly characterized. Here we provide a comprehensive overview of augurin-dependent signal transduction pathways. Because of their secreted nature and the potential to be manipulated pharmacologically, augurin and its derived peptides represent attractive targets for diagnostic development and discovery of new therapeutic agents for the human diseases resulting from the deregulation of the signaling cascades they modulate. From this perspective, the characterization of the precise nature of augurin derived peptides and the identification of the receptor(s) on the cell surface conveying augurin signaling to downstream effectors are crucial to develop agonists and antagonists for this protein. Video abstract.