OTUD7B Deubiquitinates LSD1 to Govern Its Binding Partner Specificity, Homeostasis, and Breast Cancer Metastasis

• DOI: 10.1002/advs.202004504
• Publication Date: 2021-05-29T15:24:20Z
• Authors: Zhicheng Gong; Aicun Li; Jiancheng Ding; Qing Li; Lei Zhang; Yuanpei Li; Zhe Meng; Fei Chen; Jialiang Huang; Dawang Zhou; Ronggui Hu; Jing Ye; Wen Liu; Han You
• Keywords: Corepressor

Genomic amplification of OTUD7B is frequently found across human cancers. But its role in tumorigenesis poorly understood. Lysine-specific demethylase 1 (LSD1) known to execute epigenetic regulation by forming corepressor complex with CoREST/histone deacetylases (HDACs). However, the molecular mechanisms which cells maintain LSD1/CoREST integrity are unknown. Here, it reported that LSD1 protein undergoes K63-linked polyubiquitination. responsible for deubiquitination at K226/277 residues, resulting dynamic control binding partner specificity and cellular homeostasis. deficiency increases ubiquitination LSD1, disrupts formation targets p62-mediated proteolysis. Consequently, impairs genome-wide occupancy enhances methylation H3K4/H3K9, therefore profoundly impacting global gene expression abrogating breast cancer metastasis. Moreover, physiological fluctuation modulates cell cycle-dependent oscillation, ensuring G1/S transition. Both proteins overpresented high-grade or metastatic cancer, while dysregulation either associated poor survival Thus, plays a unique partner-switching maintaining complex, turnover,