Dataset Information

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

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 substrates 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.

SUBMITTER: Gao Z

PROVIDER: S-EPMC9016840 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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

Gao Zhenfei Z Wang Anzhao A Zhao Yongxu Y Zhang Xiaoxu X Yuan Xiangshan X Li Niannian N Xu Chong C Wang Shenming S Zhu Yaxin Y Zhu Jingyu J Guan Jian J Liu Feng F Yin Shankai S

ACS omega 20220331 14

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 <i>BTBD9</i> and performed proteomic an ...[more]

PMID: 35449961

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Dataset Information

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

Publications

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

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