Biological roles of LSD1 beyond its demethylase activity

It is well-established that Lysine-specific demethylase 1 (LSD1, also known as KDM1A) roles as a lysine demethylase canonically acting on H3K4me1/2 and H3K9me1/2 for regulating gene expression. Though the discovery of non-histone substrates methylated by LSD1 has largely expanded the functions of LS...

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Published inCellular and molecular life sciences : CMLS Vol. 77; no. 17; pp. 3341 - 3350
Main Authors Gu, Feiying, Lin, Yuxin, Wang, Zhun, Wu, Xiaoxin, Ye, Zhenyue, Wang, Yuezhen, Lan, Huiyin
Format Journal Article
LanguageEnglish
Published Cham Springer International Publishing 01.09.2020
Springer Nature B.V
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Summary:It is well-established that Lysine-specific demethylase 1 (LSD1, also known as KDM1A) roles as a lysine demethylase canonically acting on H3K4me1/2 and H3K9me1/2 for regulating gene expression. Though the discovery of non-histone substrates methylated by LSD1 has largely expanded the functions of LSD1 as a typical demethylase, recent groundbreaking studies unveiled its non-catalytic functions as a second life for this demethylase. We and others found that LSD1 is implicated in the interaction with a line of proteins to exhibit additional non-canonical functions in a demethylase-independent manner. Here, we present an integrated overview of these recent literatures charging LSD1 with unforeseen functions to re-evaluate and summarize its non-catalytic biological roles beyond the current understanding of its demethylase activity. Given LSD1 is reported to be ubiquitously overexpressed in a variety of tumors, it has been generally considered as an innovative target for cancer therapy. We anticipate that these non-canonical functions of LSD1 will arouse the consideration that extending the LSD1-based drug discovery to targeting LSD1 protein interactions non-catalytically, not only its demethylase activity, may be a novel strategy for cancer prevention.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-020-03489-9