| Integrative Proteome and Ubiquitinome Analyses Reveal the Substrates of BTBD9 and Its Underlying Mechanism in Sleep Regulation |
| Author |
Gao, ZF; Wang, AZ; Zhao, YX; Zhang, XX; Yuan, XS; Li, NN; Xu, C; Wang, SM; Zhu, YX; Zhu, JY; Guan, J; Liu, F; Yin, SK |
| Journal |
ACS OMEGA |
| Pub Year |
2022 |
| Type |
Article |
| Abstract |
Ubiquitination is a major posttranslational modification of proteins that affects their stability, and E3 ligases play a key role in ubiquitination by specifically recognizing their substrates. BTBD9, an adaptor of the Cullin-RING ligase complex, is responsible for substrate recognition and is associated with sleep homeostasis. However, the substrates of BTBD9-mediated ubiquitination remain unknown. Here, we generated an SH-SY5Y cell line stably expressing BTBD9 and performed proteomic analysis combined with ubiquitinome analysis to identify the downstream targets of BTBD9. Through this approach, we identified four potential BTBD9-mediated ubiquitination su-strates that are targeted for degradation. Among these candidate substrates, inosine monophosphate dehydrogenase (IMPDH2), a novel target of BTBD9-mediated degradation, is a potential risk gene for sleep dysregulation. In conclusion, these findings not only demonstrate that proteomic analysis can be a useful general approach for the systematic identification of E3 ligase substrates but also identify novel substrates of BTBD9, providing a resource for future studies of sleep regulation mechanisms. |
| Issue |
7 |
| Volume |
7 |
