Project description:Usp22 and Usp21 are important for Foxp3 stability. We used RNA sequencing to determine the broad changes upon Usp22 and Usp21 deletionWe then performed gene expression profiling analysis using data obtained from RNA-seq and compared to each other
Project description:Regulatory T (Treg) cells harbor immune suppressive capacity and are crucial for the maintenance of peripheral tolerance. Treg cells are considered to be heterogenic, where compromised FOXP3 expression results in the generation of exTreg cells. Here we report that the E3 deubiquitinase USP21 prevents the depletion of FOXP3 protein and restricts tissue-resident exTreg cell generation. Mice lacking USP21 in Treg cells display immune disorders characterized by spontaneous T cell activation and excessive T helper type 1 (Th1) skewing. USP21 stabilizes FOXP3 protein by mediating its deubiquitination and therefore helps to maintain the expression of Treg signature genes. Moreover, at inflamed loci, tissue-resident USP21-deficient Treg cells display a Th1-like effector phenotype. Therefore, we demonstrate how USP21 controls the identity of tissue-resident Treg cells by preventing FOXP3 loss.
Project description:USP21 belongs to ubiquitin specific protease (USP) family. To dissect the molecular mechanisms that regulated by USP21 overexpression in PDAC cells, we conducted RNA-seq analysis of iKPC PDAC cells overexpressing wild-type USP21 (WT-USP21) and enzyme dead USP21 (ED-USP21).
Project description:Nanog is a master pluripotency factor of embryonic stem cells (ESCs). Stable expression of Nanog is required to maintain the stemness of ESCs, although Nanog is a short-lived protein and quickly degraded by the ubiquitin-dependent proteasome system (UPS). Here, we report that the deubiquitinase USP21 interacts with, deubiquitinates and stabilizes Nanog and therefore maintains the protein level of Nanog in mouse-ESCs (mESCs). Loss of USP21 results in Nanog destruction, mESCs differentiation and reduced the somatic cell reprogramming efficiency. USP21 is a transcriptional target of the LIF/STAT3 pathway and is downregulated upon differentiation. Moreover, differentiation cues promote ERK-mediated phosphorylation and dissociation of USP21 from Nanog, thus leading to Nanog degradation. Additionally, USP21 is recruited to gene promoters by Nanog to deubiquitinate histone H2A at K119 and thus facilitates Nanog-mediated gene expression. Together, our findings provide a regulatory mechanism by which extrinsic signals regulate mESC fate via deubiquitinating Nanog.