Background: Iron induces the immediate nuclear influx of Myb3 in T. vaginalis. Results: Iron triggered a cAMP-mediated signaling that resulted in the phosphorylation and ubiquitination of Myb3 to accelerate its nuclear influx. Conclusion: Iron triggers signal transduction to activate a rapid nuclear influx of Myb3. Significance: This work revealed a novel role of iron in poorly studied signal transduction in the parasite.