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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Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627283/ |
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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 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. |
repository_type |
Open Access Journal |
institution_category |
Foreign Institution |
institution |
US National Center for Biotechnology Information |
building |
NCBI PubMed |
collection |
Online Access |
language |
English |
format |
Online |
author |
Piao, Lianhua Suzuki, Takehiro Dohmae, Naoshi Nakamura, Yusuke Hamamoto, Ryuji |
spellingShingle |
Piao, Lianhua Suzuki, Takehiro Dohmae, Naoshi Nakamura, Yusuke Hamamoto, Ryuji SUV39H2 methylates and stabilizes LSD1 by inhibiting polyubiquitination in human cancer cells |
author_facet |
Piao, Lianhua Suzuki, Takehiro Dohmae, Naoshi Nakamura, Yusuke Hamamoto, Ryuji |
author_sort |
Piao, Lianhua |
title |
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_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_sort |
suv39h2 methylates and stabilizes lsd1 by inhibiting polyubiquitination in human cancer cells |
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. |
publisher |
Impact Journals LLC |
publishDate |
2015 |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627283/ |
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1613495319803199488 |