Project description:The goal of the experiment was to determine the role of H2A deubiquitinase in the nerve injury response in peripheral nerve. A Schwann cell specific knockout of the H2A deubiquitinase (Bap1) was generated to compare with wild type mice.
Project description:The proteasome-associated deubiquitinase USP14 has attracted significant attention in recent years due to its potential as a drug target. Here, we employ an inducible USP14 knockout system to dissect early phenotypic and gene expression alterations following USP14 loss. Transcriptomic analysis revealed widespread changes in the expression of actin cytoskeleton components associated with shifts in cellular actin distribution and morphology, as well as changes in the deubiquitinase expression profile. We observed an increase in ubiquitin turnover that appeared to be offset by the upregulation of polyubiquitin genes UBB and UBC.
Project description:Ubiquitination-mediated protein degradation of key transcriptional factors is important to the self-renewal of embryonic stem (ES) cells. However, little is known about the deubiquitination in ES self-renewal and differentiation. Here, we report that deubiquitinase USP21 is an important positive regulator to keep ES cells under undifferentiation stasus by deubiquitination and stabilization of Nanog, a key transcriptional factor of ES cells. Loss of USP21 led to ES cells differentiation and defect in reprogramming.
Project description:The identification of key factors involved in pathological cardiac hypertrophy is crucial to exploring novel treatments for heart failure. In this study, we elucidated the role of Ubiquitin-specific protease 29 (USP29), a deubiquitinase, in pressure overload-induced cardiac hypertrophy. Genetic knockout of USP29 in mice significantly exacerbated TAC-induced heart hypertrophy, dysfunction, and fibrosis; whereas overexpression of USP29 in cardiomyocytes attenuated the hypertrophic response. Similarly, USP29 markedly alleviated PE-induced hypertrophy of primary neonatal rat cardiomyocytes. Mechanistically, the cardio-protective effects mediated by USP29 were attributed to its suppression of transforming growth factor β-activated kinase 1 (TAK1)-JNK/P38 signaling pathway activation. Collectively, our study suggests that targeting either USP29 or its interaction with TAK1 could represent an innovative therapeutic strategy for treating heart failure and cardiac hypertrophy.