SUV39H2 methylates and stabilizes LSD1 by inhibiting polyubiquitination in human cancer cells

LSD1 is a histone lysine demethylase, which is highly expressed in multiple types of human cancer. Although its roles in transcriptional regulation have been well-studied, functional regulation of LSD1 by post-translational modifications still remains unknown. Here, we demonstrate that the histone l...

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Detalles Bibliográficos
Autores principales: Piao, Lianhua, Suzuki, Takehiro, Dohmae, Naoshi, Nakamura, Yusuke, Hamamoto, Ryuji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Priority Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627283/
https://www.ncbi.nlm.nih.gov/pubmed/26183527
Descripción
Sumario:LSD1 is a histone lysine demethylase, which is highly expressed in multiple types of human cancer. Although its roles in transcriptional regulation have been well-studied, functional regulation of LSD1 by post-translational modifications still remains unknown. Here, we demonstrate that the histone lysine methyltransferase SUV39H2 trimethylated LSD1 on lysine 322. Knockdown of SUV39H2 resulted in a decrease of LSD1 protein even though the mRNA levels were unchanged. SUV39H2-induced LSD1 methylation suppresses LSD1 polyubiquitination and subsequent degradation. In addition, we also observed indirect effect of SUV39H2 overexpression on LSD1-target genes. Our results reveal the regulatory mechanism of LSD1 protein through its lysine methylation by SUV39H2 in human cancer cells.

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