Ubiquitination plays a key role in an insecticide resistance fitness cost

Ubiquitination is an essential posttranslational modification in eukaryotes, which plays a fundamental role in numerous important biological functions. However, the role of ubiquitination in the evolution of adaptive traits in insects remains poorly understood. Here, we reveal the role of ubiquitination in insecticide resistance and its associated fitness cost in the whitefly pest, Bemisia tabaci . We identify the RING-type E3 ubiquitin ligase TRIM37 in B. tabaci and show its promotion of ubiquitination in vivo and in vitro. We further demonstrate that this ligase binds to other ubiquitin enzymes as part of the E1-1/E2-3/TRIM37 ubiquitination cascade, negatively regulating the transcription factor CREB by marking it for degradation. CREB, in turn, positively regulates the insecticide resistance gene CYP6CM1 while negatively regulating the key oogenesis gene Vasa . Downregulation of TRIM37 in neonicotinoid-resistant B. tabaci strains enhances insecticide detoxification via CYP6CM1 upregulation, but concurrently incurs a reproductive fitness cost due to downstream Vasa suppression. Our findings advance understanding of the insect ubiquitination system and its role in adaptive processes, while offering insights for sustainable pest control strategies.