title: 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.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Lianhua
authors.initials: L
authors.lastname: Piao
authors.affiliation: Biomolecular Characterizaion Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Biomolecular Characterizaion Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hamamoto
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D056466:Histone Demethylases / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D008745:Methylation; D051379:Mice; D009369:Neoplasms / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D054875:Ubiquitination
chemical_list: D056466:Histone Demethylases; C495195:KDM1A protein, human; D011495:Histone-Lysine N-Methyltransferase; C515701:SUV39H2 protein, human
keywords: LSD1; SUV39H2; carcinogenesis; non-histone protein methylation