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...
Saved in:
Published in | Cellular and molecular life sciences : CMLS Vol. 77; no. 17; pp. 3341 - 3350 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Cham
Springer International Publishing
01.09.2020
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
Cover
Loading…
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 |