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

ABSTRACT: 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.

SUBMITTER: Piao L

PROVIDER: S-EPMC4627283 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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

Piao Lianhua L Suzuki Takehiro T Dohmae Naoshi N Nakamura Yusuke Y Hamamoto Ryuji R

Oncotarget 20150701 19

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 methylati ...[more]

PMID: 26183527

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