Mechanisms and functions of Nrf2 signaling in Drosophila

• Published in: Free radical biology & medicine 2015-11, Vol.88 (Pt B), p.302-313
• Main Authors: Pitoniak, Andrew, Bohmann, Dirk
• Format: Article
• Language: English
• Subjects: Aging; Aging - physiology; Animals; Drosophila; Drosophila - metabolism; Drosophila Proteins - metabolism; Embryonic Development - physiology; Free radicals; Keap1; Maf-S; Nrf2; Oxidative stress; Oxidative Stress - physiology; Repressor Proteins - metabolism; Signal Transduction - physiology
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2015.06.020

The Nrf2 transcription factor belongs to the Cap’n’collar family, named after the founding member of this group, the product of the Drosophila Cap’n’collar gene. The encoded protein, Cap’n’collar, abbreviated Cnc, offers a convenient and accessible model to study the structure, function, and biology of Nrf2 transcription factors at the organismic, tissular, cellular, and molecular levels, using the powerful genetic, genomic, and biochemical tools available in Drosophila. In this review we provide an account of the original identification of Cnc as a regulator of embryonic development. We then describe the discovery of Nrf2-like functions of Cnc and its role in acute stress signaling and aging. The establishment of Drosophila as a model organism in which the mechanisms and functions of Nrf2 signaling can be studied has led to several discoveries: the regulation of stem cell activity by an Nrf2-mediated redox mechanism, the interaction of Nrf2 with p62 and Myc in the control of tissue growth and the unfolded protein response, and more. Several of these more recent lines of investigation are highlighted. Model organisms such as the fly and the worm remain powerful experimental platforms that can help to unravel the many remaining puzzles regarding the role of Nrf2 and its relatives in controlling the physiology and maintaining the health of multicellular organisms. [Display omitted] •The Drosophila cnc gene encodes homologs of mammalian Nrf1 and Nrf2.•Other components of Nrf2 signaling such as Keap1 and Maf-S are conserved in Drosophila.•Genetic programs controlled by Drosophila Nrf2 resemble those in mammals.•Drosophila Nrf2 has complex functions controlling development and homeostasis.•Drosophila provides a model to study molecular and organismic functions of Nrf2.