Fig. 7
From: PHF20L1 antagonizes SOX2 proteolysis triggered by the MLL1/WDR5 complexes
The expression of SOX2 is closely related to aggressive teratoma and is negatively correlated to WDR5 expression. a The changes of SOX2 protein level modulated the transcriptional activity of SOX2. The mRNA levels of SOX17, FOXA2, KRT6A, and TP63 were RT-PCR-examined after interference of MLL1 or PHF20L1. b The ChIP assay of SOX2 on the promotor regions of SOX17, FOXA2, KRT6A, and TP63 after knockdown of MLL1, SOX2, or PHF20L1. a and b *p < 0.05, **p < 0.01, ***p < 0.001. The data were represented as mean ± SD. c Representative images of tissue microarray and IHC staining of SOX2, WDR5, and PHF20L1 in ovarian teratoma. Bar: 100 μm (20 μm for magnified images). d Silencing of PHF20L1 impaired the colony formation of PA-1 cells. Upper panel: representative images of colonies formed in agar under microscope. Bar: 500 μm. Lower panel: representative wells showing colonies stained by 0.05% crystal violet. e Silencing of PHF20L1 slowed the growth of tumors in NOD/SCID mice. Left panel: representative mouse transplanted with PA-1 cells for 28 days. Left side was subcutaneously injected with 5 × 106 cells treated with LUC siRNAs and right side was transplanted with 5 × 106 cells treated with PHF20L1 or MLL1 siRNAs. Middle panel: tumors detached from NOD/SCID mice. Right panel: the volumes of tumors were measured and plotted. f Illustrated model for the antagonizing regulation on the protein stability of SOX2 co-played by the MLL1/WDR5 complexes and PHF20L1. The methyltransferase complexes MLL1/WDR5 possibly methylates SOX2 at lysine 42 (K42) and promotes its ubiquitination and 26S proteasome-mediated degradation. In contrast, PHF20L1 may recognizes the methylated K42 (K42me) on SOX2 and prevent it from ubiquitin-dependent degradation
