ArticleLaboratory investigation; a journal of technical methods and pathology2018
PHF20L1 antagonizes SOX2 proteolysis triggered by the MLL1/WDR5 complexes.
Article in Laboratory investigation; a journal of technical methods and pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 14 citations in OpenAlex.
- A revised model for PHF20L1 Tudor function: DNA binding overrides methylation selectivity on nucleosomes.The Journal of biological chemistry · 2026Article
- PHF20L1: An Epigenetic Regulator in Cancer and Beyond.Biomolecules · 2025Review
- Histone methyltransferase MLL1 drives renal tubular cell apoptosis by p53-dependent repression of E-cadherin during cisplatin-induced acute kidney injury.Cell death & disease · 2022Article
- PHD finger protein 20-like protein 1 (PHF20L1) in ovarian cancer: from its overexpression in tissue to its upregulation by the ascites microenvironment.Cancer cell international · 2022Article
- High Expression of the SdCells · 2020Article
- Proteolysis of methylated SOX2 protein is regulated by L3MBTL3 and CRL4The Journal of biological chemistry · 2019Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Transcriptional factor SOX2 regulates stem cell pluripotency, cell differentiation and tumorigenesis. As a key factor, the expression of SOX2 is tightly regulated at transcriptional and post-translational levels. However, the underlying mechanism of SOX2 protein stability remains to be elucidated. Here we show that the histone-lysine N-methyltransferase MLL1/WDR5 complexes physically interact with SOX2 and evoke SOX2 proteolysis, possibly through methylation on a potential site lysine 42 (K42). Small interfering RNA (siRNA)-mediated gene silencing of the components of the MLL1/WDR5 complexes WDR5, MLL1, RBBP5, and ASH2L lead to the accumulation of SOX2, while forced expression of WDR5 promotes SOX2 ubiquitination and proteolysis. Conversely, PHD finger protein 20-like protein 1 (PHF20L1) associates with SOX2, antagonizes SOX2 ubiquitination and the sequential degradation induced by the MLL1/WDR5 complexes. RNA interferences of PHF20L1 promote the degradation of SOX2, while forced expression of PHF20L1 stabilizes SOX2. Co-silencing of MLL1/WDR5 components and PHF20L1 preclude degradation of SOX2 induced by knockdown of PHF20L1. Moreover, co-expression of PHF20L1 and WDR5 prevent ubiquitination of SOX2 triggered by WDR5 over-expression. However, SOX2 mutant K42R is non-sensitive to the MLL1/WDR5 complexes or PHF20L1. In addition, PHF20L1 may regulate the stability of SOX2 through its malignant brain tumor (MBT) domain, since the degradation of SOX2 is accelerated by UNC1215 and UNC669, inhibitors that bind to the MBT domain. Furthermore, abundant expression of SOX2 is highly correlated to immature ovarian teratoma. Loss of PHF20L1 weakened the tumor initiation ability of PA-1 cells while ablation of MLL1 promoted the growth of tumors. Thus, our studies reveal an antagonistic mechanism by which the protein stability of SOX2 is regulated by the MLL1/WDR5 complexes and PHF20L1, possibly through methylation of SOX2 protein, and provide a novel perspective on SOX2-positive cancer treatment.
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