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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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
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author Piao, Lianhua
Suzuki, Takehiro
Dohmae, Naoshi
Nakamura, Yusuke
Hamamoto, Ryuji
author_facet Piao, Lianhua
Suzuki, Takehiro
Dohmae, Naoshi
Nakamura, Yusuke
Hamamoto, Ryuji
author_sort Piao, Lianhua
collection PubMed
description 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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spelling pubmed-46272832015-12-02 SUV39H2 methylates and stabilizes LSD1 by inhibiting polyubiquitination in human cancer cells Piao, Lianhua Suzuki, Takehiro Dohmae, Naoshi Nakamura, Yusuke Hamamoto, Ryuji Oncotarget Priority Research Paper 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. Impact Journals LLC 2015-07-03 /pmc/articles/PMC4627283/ /pubmed/26183527 Text en Copyright: © 2015 Piao et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Priority Research Paper
Piao, Lianhua
Suzuki, Takehiro
Dohmae, Naoshi
Nakamura, Yusuke
Hamamoto, Ryuji
SUV39H2 methylates and stabilizes LSD1 by inhibiting polyubiquitination in human cancer cells
title SUV39H2 methylates and stabilizes LSD1 by inhibiting polyubiquitination in human cancer cells
title_full SUV39H2 methylates and stabilizes LSD1 by inhibiting polyubiquitination in human cancer cells
title_fullStr SUV39H2 methylates and stabilizes LSD1 by inhibiting polyubiquitination in human cancer cells
title_full_unstemmed SUV39H2 methylates and stabilizes LSD1 by inhibiting polyubiquitination in human cancer cells
title_short SUV39H2 methylates and stabilizes LSD1 by inhibiting polyubiquitination in human cancer cells
title_sort suv39h2 methylates and stabilizes lsd1 by inhibiting polyubiquitination in human cancer cells
topic Priority Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627283/
https://www.ncbi.nlm.nih.gov/pubmed/26183527
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