Integrative Proteome and Ubiquitinome Analyses Reveal the Substrates of BTBD9 and Its Underlying Mechanism in Sleep Regulation

• DOI: 10.1021/acsomega.1c07262
• Publication Date: 2022-03-31T14:04:05Z
• Authors: Zhenfei Gao; Anzhao Wang; Yongxu Zhao; Xiaoxu Zhang; Xiangshan Yuan; Niannian Li; Chong Xu; Shenming Wang; Yaxin Zhu; Jingyu Zhu; Jian Guan; Feng Liu; Shankai Yin
• Keywords: Cullin; Proteome; Post-translational regulation; F-box protein; Protein Degradation

Ubiquitination is a major posttranslational modification of proteins that affects their stability, and E3 ligases play key role in ubiquitination by specifically recognizing substrates. BTBD9, an adaptor the Cullin-RING ligase complex, responsible for substrate recognition associated with sleep homeostasis. However, substrates BTBD9-mediated remain unknown. Here, we generated SH-SY5Y cell line stably expressing BTBD9 performed proteomic analysis combined ubiquitinome to identify downstream targets BTBD9. Through this approach, identified four potential are targeted degradation. Among these candidate substrates, inosine monophosphate dehydrogenase (IMPDH2), novel target degradation, risk gene dysregulation. In conclusion, findings not only demonstrate can be useful general approach systematic identification but also providing resource future studies regulation mechanisms.