Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8295770 | Biochemical and Biophysical Research Communications | 2018 | 5 Pages |
Abstract
The C2H2 type zinc-finger transcription factor Nerfin-1 expresses dominantly in Drosophila nervous system and plays an important role in early axon guidance decisions and preventing neurons dedifferentiation. Recently, increasing reports indicated that INSM1 (homologue to nerfin-1 in mammals) is a useful marker for prognosis of neuroendocrine tumors. The dynamic expression of Nerfin-1 is regulated post-transcriptionally by multiple microRNAs; however, its post-translational regulation is still unclear. Here we showed that the protein turnover of Nerfin-1 is regulated by Slimb, the substrate adaptor of SCFSlimb ubiquitin ligase complex. Mechanistically, Slimb associates with Nerfin-1 and promotes it ubiquitination and degradation in Drosophila S2R+ cells. Furthermore, we determined that the C-terminal half of Nerfin-1 (Nerfin-1CT) is required for its binding to Slimb. Genetic epistasis assays showed that Slimb misexpression antagonizes, while knock-down enhances the activity of Nerfin-1CT in Drosophila eyes. Our data revealed a new link to understand the underlying mechanism for Nerfin-1 turnover in post-translational level, and provided useful insights in animal development and disease treatment by manipulating the activity of Slimb and Nerfin-1.
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Authors
Xiaohui Lin, Feng Wang, Yuanpei Li, Chaojun Zhai, Guiping Wang, Xiaoting Zhang, Yang Gao, Tao Yi, Dan Sun, Shian Wu,