ArticleThe Journal of biological chemistry2018
LSD1 demethylase and the methyl-binding protein PHF20L1 prevent SET7 methyltransferase-dependent proteolysis of the stem-cell protein SOX2.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Development of a prognostic prediction model incorporatingJournal of gastrointestinal oncology · 2026Article
- SUV39H1 facilitate the osteogenic differentiation of dental pulp stem cells by modulating lipid metabolism and mitochondrial dynamics through FASN via non-histone methylation and ubiquitination mechanism.Stem cell research & therapy · 2025Article
- PHF20L1: An Epigenetic Regulator in Cancer and Beyond.Biomolecules · 2025Review
- Key roles of ubiquitination in regulating critical regulators of cancer stem cell functionality.Genes & diseases · 2025Review
- Lysine methyltransferase SETD7 in cancer: functions, molecular mechanisms and therapeutic implications.Molecular biology reports · 2025Review
- Lysine and arginine methylation of transcription factors.Cellular and molecular life sciences : CMLS · 2024Review
- Lysine-specific methyltransferase Set7/9 in stemness, differentiation, and development.Biology direct · 2024Review
- WSB1/2 target chromatin-bound lysine-methylated RelA for proteasomal degradation and NF-κB termination.Nucleic acids research · 2024Article
- Lysine Methylation-Dependent Proteolysis by the Malignant Brain Tumor (MBT) Domain Proteins.International journal of molecular sciences · 2024Review
- Article
- RNA in situ conformation sequencing reveals novel long-range RNA structures with impact on splicing.RNA (New York, N.Y.) · 2023Article
- The assembly of mammalian SWI/SNF chromatin remodeling complexes is regulated by lysine-methylation dependent proteolysis.Nature communications · 2022Article
- Review
- The Epigenetic Regulation of Nonhistone Proteins by SETD7: New Targets in Cancer.Frontiers in genetics · 2022Review
- Lysine demethylase LSD1 delivered via small extracellular vesicles promotes gastric cancer cell stemness.EMBO reports · 2021Article
- Roles of lysine-specific demethylase 1 (LSD1) in homeostasis and diseases.Journal of biomedical science · 2021Review
- Histone Methylation Related Therapeutic Challenge in Cardiovascular Diseases.Frontiers in cardiovascular medicine · 2021Review
- Functional characterization of SOX2 as an anticancer target.Signal transduction and targeted therapy · 2020Review
- Inhibition of LSD1 promotes the differentiation of human induced pluripotent stem cells into insulin-producing cells.Stem cell research & therapy · 2020Article
- Growth Factor Independence 1B-Mediated Transcriptional Repression and Lineage Allocation Require Lysine-Specific Demethylase 1-Dependent Recruitment of the BHC Complex.Molecular and cellular biology · 2019Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
The pluripotency-controlling stem-cell protein SRY-box 2 (SOX2) plays a pivotal role in maintaining the self-renewal and pluripotency of embryonic stem cells and also of teratocarcinoma or embryonic carcinoma cells. SOX2 is monomethylated at lysine 119 (Lys-119) in mouse embryonic stem cells by the SET7 methyltransferase, and this methylation triggers ubiquitin-dependent SOX2 proteolysis. However, the molecular regulators and mechanisms controlling SET7-induced SOX2 proteolysis are unknown. Here, we report that in human ovarian teratocarcinoma PA-1 cells, methylation-dependent SOX2 proteolysis is dynamically regulated by the LSD1 lysine demethylase and a methyl-binding protein, PHD finger protein 20-like 1 (PHF20L1). We found that LSD1 not only removes the methyl group from monomethylated Lys-117 (equivalent to Lys-119 in mouse SOX2), but it also demethylates monomethylated Lys-42 in SOX2, a reaction that SET7 also regulated and that also triggered SOX2 proteolysis. Our studies further revealed that PHF20L1 binds both monomethylated Lys-42 and Lys-117 in SOX2 and thereby prevents SOX2 proteolysis. Down-regulation of either LSD1 or PHF20L1 promoted SOX2 proteolysis, which was prevented by SET7 inactivation in both PA-1 and mouse embryonic stem cells. Our studies also disclosed that LSD1 and PHF20L1 normally regulate the growth of pluripotent mouse embryonic stem cells and PA-1 cells by preventing methylation-dependent SOX2 proteolysis. In conclusion, our findings reveal an important mechanism by which the stability of the pluripotency-controlling stem-cell protein SOX2 is dynamically regulated by the activities of SET7, LSD1, and PHF20L1 in pluripotent stem cells.
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