Histone methyl-transferases and demethylases in the autophagy regulatory network: the emerging role of KDM1A/LSD1 demethylase

Ambrosio, Susanna; Ballabio, Andrea; Majello, Barbara

doi:10.1080/15548627.2018.1520546

Cited by 22 publications

(17 citation statements)

References 111 publications

(142 reference statements)

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“…LSD1 as an epigenetic regulator of the autophagic pathway is pivotal in protecting oocytes from massive loss. Studies including ours have proved that LSD1 localizes to the nucleus of cells (Kahl et al, ; Lim et al, ) and is critical for the negative regulation of genes essential for the autophagic process by recruiting to the promoters of genes like Atg3 , Atg10 , transcription factor EB ( Tfeb) , sestrin 2 ( Sesn2 ), and p62 (Ambrosio, Ballabio, & Majello, ; Ambrosio & Majello, ; Ambrosio et al, ; Byun et al, ; Periz et al, ; Sardiello et al, ; Settembre et al, ; Wang, Long, et al, ). LSD1 importing to the nucleus is related to its N‐terminal nuclear localization signal motifs (Jin et al, ).…”

Section: Discussionmentioning

confidence: 90%

“…to the promoters of genes like Atg3, Atg10, transcription factor EB (Tfeb), sestrin 2 (Sesn2), and p62 (Ambrosio, Ballabio, & Majello, 2019;Ambrosio et al, 2017;Byun et al, 2017;Periz et al, 2015;Sardiello et al, 2009;Settembre et al, 2011;Wang, Long, et al, 2017). LSD1 importing to the nucleus is related to its N-terminal nuclear localization signal motifs (Jin et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

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LSD1 contributes to programmed oocyte death by regulating the transcription of autophagy adaptor SQSTM1/p62

Zhang

Zhu

et al. 2020

Aging Cell

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In female mammals, the size of the initially established primordial follicle (PF) pool within the ovaries determines the reproductive lifespan of females. Interestingly, the establishment of the PF pool is accompanied by a remarkable programmed oocyte loss for unclear reasons. Although apoptosis and autophagy are involved in the process of oocyte loss, the underlying mechanisms require substantial study. Here, we identify a new role of lysine‐specific demethylase 1 (LSD1) in controlling the fate of oocytes in perinatal mice through regulating the level of autophagy. Our results show that the relatively higher level of LSD1 in fetal ovaries sharply reduces from 18.5 postcoitus (dpc). Meanwhile, the level of autophagy increases while oocytes are initiating programmed death. Specific disruption of LSD1 resulted in significantly increased autophagy and obviously decreased oocyte number compared with the control. Conversely, the oocyte number is remarkably increased by the overexpression of Lsd1 in ovaries. We further demonstrated that LSD1 exerts its role by regulating the transcription of p62 and affecting autophagy level through its H3K4me2 demethylase activity. Finally, in physiological conditions, a decrease in LSD1 level leads to an increased level of autophagy in the oocyte when a large number of oocytes are being lost. Collectively, LSD1 may be one of indispensible epigenetic molecules who protects oocytes against preterm death through repressing the autophagy level in a time‐specific manner. And epigenetic modulation contributes to programmed oocyte death by regulating autophagy in mice.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

LSD1 contributes to programmed oocyte death by regulating the transcription of autophagy adaptor SQSTM1/p62

Zhang

Zhu

et al. 2020

Aging Cell

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“…A large number of studies have highlighted the pivotal role of LSD1 in several cellular processes in normal and cancer cells such as control of stemness, differentiation [12,22,23], cell motility, epithelial-to-mesenchymal transition [10,25,26], autophagy [9,27], senescence [28], neurodegenerative diseases [29,30], and metabolism [31]. To achieve these widespread biological functions, LSD1 is a component of different multi-protein complexes and its association with over 60 gene regulatory proteins has been demonstrated [14,15,32,33,34].…”

Section: Introductionmentioning

confidence: 99%

Expanding the Role of the Histone Lysine-Specific Demethylase LSD1 in Cancer

Majello

Gorini

Saccà

et al. 2019

Cancers

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105

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Studies of alterations in histone methylation in cancer have led to the identification of histone methyltransferases and demethylases as novel targets for therapy. Lysine-specific demethylase 1 (LSD1, also known as KDM1A), demethylates H3K4me1/2, or H3K9me1/2 in a context-dependent manner. In addition to the well-studied role of LSD1 in the epigenetic regulation of histone methylation changes, LSD1 regulates the methylation dynamic of several non-histone proteins and participates in the assembly of different long noncoding RNA (lncRNA_ complexes. LSD1 is highly expressed in various cancers, playing a pivotal role in different cancer-related processes. Here, we summarized recent findings on the role of LSD1 in the regulation of different biological processes in cancer cells through dynamic methylation of non-histone proteins and physical association with dedicated lncRNA.

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“…Lysine‐specific demethylase 1 (LSD1) is the first enzyme identified to be capable of removing the methyl group from methylated lysines in histone proteins. LSD1 reportedly demethylates histone H3 on Lys4 (H3K4) and on Lys9 (H3K9) and PGC‐1α is methylated by SET7/9 and demethylated by LSD1 at Lys779.…”

Section: Posttranslational Modification Of Pgc‐1αmentioning

confidence: 99%

Posttranslational regulation of PGC‐1α and its implication in cancer metabolism

Luo

Liao

Quan

et al. 2019

Intl Journal of Cancer

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Deregulation of cellular metabolism is well established in cancer. The mitochondria are dynamic organelles and act as the center stage for energy metabolism. Central to mitochondrial regulatory network is peroxisome proliferator‐activated receptor γ coactivator 1a (PGC‐1α), which serves as a master regulator of mitochondrial proliferation and metabolism. The activity and stability of PGC‐1α are subject to dynamic and versatile posttranslational modifications including phosphorylation, ubiquitination, methylation and acetylation in response to metabolic stress and other environmental signals. In this review, we describe the structure of PGC‐1α. Then, we discuss recent advances in the posttranslational regulatory machinery of PGC‐1α, which affects its transcriptional activity, stability and organelle localization. Furthermore, we address the important roles of PGC‐1α in tumorigenesis and malignancy. Finally, we also mention the clinical therapeutic potentials of PGC‐1α modulators. A better understanding of the elegant function of PGC‐1α in cancer progression could provide novel insights into therapeutic interventions through the targeting of PGC‐1α signaling.

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Histone methyl-transferases and demethylases in the autophagy regulatory network: the emerging role of KDM1A/LSD1 demethylase

Cited by 22 publications

References 111 publications

LSD1 contributes to programmed oocyte death by regulating the transcription of autophagy adaptor SQSTM1/p62

LSD1 contributes to programmed oocyte death by regulating the transcription of autophagy adaptor SQSTM1/p62

Expanding the Role of the Histone Lysine-Specific Demethylase LSD1 in Cancer

Posttranslational regulation of PGC‐1α and its implication in cancer metabolism

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