Regulation of AP-1 by MAPK Signaling in Metal-Stressed Sea Anemone

Maayan Agron, Vera Brekhman, David Morgenstern, Tamar Lotan

Research output: Contribution to journalArticlepeer-review


Background/Aims: AP-1 transcription factor plays a conserved role in the immediate response to stress. Activation of AP-1 members jun and fos is mediated by complex signaling cascades to control cell proliferation and survival. To understand the evolution of this broadly-shared pathway, we studied AP-1 regulation by MAPK signaling in a basal metazoan. Methods: Metal-stressed cnidarian Nematostella vectensis anemones were tested with kinase inhibitors and analyzed for gene expression levels and protein phosphorylation. Results: We show that in cnidarian, AP-1 is regulated differently than in bilaterian models. ERK2 and ERK5, the main MAPK drivers of AP-1 activation in Bilateria, down-regulated fos1 and jun1 transcription in anemones exposed to metal stress, whereas p38 MAPK, triggered transcription of jun1 but not fos1. Furthermore, our results reveal that GSK3-β is the main driver of the immediate stress response in Nematostella. GSK3-β triggered transcription of AP-1 and two other stress-related genes, egr1 and hsp70. Finally, phylogenetic analysis and protein characterization show that while MAPKs and GSK3-β are evolutionarily conserved, Fos and Jun proteins in Nematostella and other cnidarians lack important regulatory and phosphorylation sites found in Bilateria. Conclusion: These findings reveal alternative network interactions of conserved signaling kinases, providing insight into the evolutionary plasticity of immediate stress response mechanisms.

Original languageEnglish
Pages (from-to)952-964
Number of pages13
JournalCellular Physiology and Biochemistry
Issue number3
StatePublished - 27 Jun 2017

Bibliographical note

Publisher Copyright:
© 2017 The Author(s). Published by S. Karger AG, Basel.


  • AP-1
  • Cnidaria
  • Evolution
  • GSK3-β
  • MAPK
  • Nematostella vectensis
  • Stress

ASJC Scopus subject areas

  • Physiology


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