Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P62988 (Ubiquitin)
4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Ubiquitin--specific protease 22 (USP22) is a new putative cancer stem cell marker, which plays a significant role in tumorigenesis and cell--cycle progression. However, little is known about the impact of USP22 knock--down on the growth of human hepatoma cell lines. In this study, elevated expression of USP22 was observed in the human HepG2 hepatic cancer cell line compared to the normal human hepatocyte Chang liver cell line. Subsequently, we used siRNA specifically suppressing expression of USP22 and observed that the knock--down of USP22 could effectively induce cell cycle arrest and inhibit HepG2 cell proliferation. Furthermore, our results showed that USP22 deletion caused down--regulation of cyclin D2 expression and up--regulation of p15 and p21 expression. Collectively, Our findings indicate that USP22 may be responsible for HepG2 cell growth and USP22 regulates the cell cycle via the c--Myc/cyclin D2 pathway and down--regulating p15 and p21 expression in HepG2 cell.
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PMID:Knock-down of USP22 by small interfering RNA interference inhibits HepG2 cell proliferation and induces cell cycle arrest. 2321 40

Ubiquitin-specific protease 22 (USP22) can regulate the cell cycle and apoptosis in many cancer cell types, while it is still unclear whether the deubiquitinating enzyme activity of USP22 is necessary for these processes. As little is known about the impact of USP22 on the growth of HeLa cell, we observed whether USP22 can effectively regulate HeLa cell growth as well as the necessity of deubiquitinating enzyme activity for these processes in HeLa cell. In this study, we demonstrate that USP22 can regulate cell cycle but not apoptosis in HeLa cell. The deubiquitinating enzyme activity of USP22 is necessary for this process as confirmed by an activity-deleted mutant (C185S) and an activity-decreased mutant (Y513C). In addition, the deubiquitinating enzyme activity of USP22 is related to the levels of BMI-1, c-Myc, cyclin D2 and p53. Our findings indicate that the deubiquitinating enzyme activity of USP22 is necessary for regulating HeLa cell growth, and it promotes cell proliferation via the c-Myc/cyclin D2, BMI-1 and p53 pathways in HeLa cell.
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PMID:The deubiquitinating enzyme activity of USP22 is necessary for regulating HeLa cell growth. 2614 14

Ubiquitin-specific protease 12 (USP12) plays a significant role in tumor cell apoptosis and cell cycle progression. However, the regulatory mechanism of USP12 in human cervical carcinoma HeLa cell growth is unknown. In this study, we showed that knockdown of USP12 effectively induced cell cycle arrest in HeLa cells and decreased BMI-1, c-Myc and cyclin D2 transcription levels. By contrast, unlike the inactive C48S mutant, over-expression of USP12 and the deubiquitinase activity enhanced L153S and R237C mutants, had the opposite effects. Interestingly, compared to wild-type, the L153S mutant resulted in a more effective cell cycle-promotion and increased BMI-1, c-Myc and cyclin D2 transcript levels. In addition to BMI-1, USP12 R237C exhibited a functional resemblance to the wild-type by involving c-Myc and cyclin D2. The effect of USP12 on HeLa cell apoptosis was not observed in our study. These results suggest that USP12 may be responsible for HeLa cell growth by affecting cell cycle progression.
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PMID:USP12 regulates cell cycle progression by involving c-Myc, cyclin D2 and BMI-1. 2668 Jan 2

Ubiquitin-specific protease 22 (USP22) aberrance has been implicated in several malignancies; however, whether USP22 plays a role in anaplastic thyroid carcinoma (ATC) remains unclear. Here, we report that USP22 expression is highly elevated in ATC tissues, which positively correlated with tumor size, extracapsular invasion, clinical stages, and poor prognosis of ATC patients. In vitro assays showed that USP22 depletion suppressed ATC cell survival and proliferation by decreasing Rb phosphorylation and cyclin D2, inactivating Akt, and simultaneously upregulating Rb; USP22 silencing restrained cell migration and invasion by inhibiting epithelial-mesenchymal transition; USP22 knockdown promoted mitochondrion- mediated and caspase-dependent apoptosis by upregulating Bax and Bid and promoting caspase-3 activation. Consistent with in vitro findings, downregulation of USP22 in ATC cells impeded tumor growth and lung metastasis in vivo. These results raise the applicability for USP22 as a useful predictor of ATC prognosis and a potential therapeutic target for ATC.
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PMID:Targeting ubiquitin-specific protease 22 suppresses growth and metastasis of anaplastic thyroid carcinoma. 2714 78