Akirin proteins in development and disease: critical roles and mechanisms of action
- PDF / 1,974,367 Bytes
- 18 Pages / 595.276 x 790.866 pts Page_size
- 22 Downloads / 169 Views
Cellular and Molecular Life Sciences
REVIEW
Akirin proteins in development and disease: critical roles and mechanisms of action Peter J. Bosch1 · Stacey L. Peek2 · Sarit Smolikove3 · Joshua A. Weiner1 Received: 11 January 2020 / Revised: 5 April 2020 / Accepted: 15 April 2020 © Springer Nature Switzerland AG 2020
Abstract 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 impor‑ tant 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. Keywords BAF · Cancer · Cell cycle · Embryonic · Myogenesis · Neurodevelopment · NFκB · Nucleus
Introduction
Peter J. Bosch and Stacey L. Peek contributed equally to this article. * Joshua A. Weiner joshua‑[email protected] Peter J. Bosch peter‑[email protected] Stacey L. Peek stacey‑[email protected] Sarit Smolikove sarit‑[email protected] 1
Department of Biology and Iowa Neuroscience Institute, University of Iowa, 143 Biology Building, Iowa City, IA 52242, USA
2
Interdisciplinary Graduate Program in Neuroscience, Department of Biology and Iowa Neuroscience Institute, University of Iowa, 143 Biology Building, Iowa City, IA 52242, USA
3
Department of Biology, University of Iowa, 143 Biology Building, Iowa City, IA 52242, USA
Akirins have recently emerged as critical regulators of mul‑ tiple developmental processes by acting as modulators of gene expression patterns. Although these small, highly con‑ served, primarily nuclear proteins remain somewhat enig‑ matic, recent studies in a host of systems including Caenorhabditis elegans (C. elegans), Drosophila melanogaster, Xenopus laevis, mice, rats, and humans have resulted in a better understanding of their functional roles and some of the mechanisms through which they act. Here, we broadly review the field to summarize our current understanding of Akirin biology, including the genes they regulate and the protein–protein interactions in which they engage. We focus particularly on recent research demonstr
Data Loading...
