Akirin proteins in development and disease: critical roles and mechanisms of action

摘要

The Akirin genes, which encode small, nuclear proteins, were first characterized in 2008 in Drosophila and rodents. Early studies demonstrated important roles in immune responses and tumorigenesis, which subsequent work found to be highly conserved. More recently, a multiplicity of Akirin functions, and the associated molecular mechanisms involved, have been uncovered. Here, we comprehensively review what is known about invertebrate Akirin and its two vertebrate homologues Akirin1 and Akirin2, highlighting their role in regulating gene expression changes across a number of biological systems. We detail essential roles for Akirin family proteins in the development of the brain, limb, and muscle, in meiosis, and in tumorigenesis, emphasizing associated signaling pathways. We describe data supporting the hypothesis that Akirins act as a "bridge" between a variety of transcription factors and major chromatin remodeling complexes, and discuss several important questions remaining to be addressed. In little more than a decade, Akirin proteins have gone from being completely unknown to being increasingly recognized as evolutionarily conserved mediators of gene expression programs essential for the formation and function of animals.