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)

Ubiquitin-specific protease 42 (USP42) is a member of deubiquitinating enzymes (DUBs). The alterations of DUBs are implicated in the pathogenesis of a wide variety of tumors. However, there are few studies on the expression and biological function of USP42 in gastric cancer (GC). Here, the expression levels of USP42 were significantly higher in GC tissues than in non-tumorous tissues. USP42 expression was significantly correlated with tumor size, TNM stage, lymph node metastasis and overall survival of patients with GC. Moreover, USP42 silencing in two GC cell lines, AGS and MKN-45, notably inhibited cell proliferation, but stimulated G1 phase arrest. The proteins promoting cell cycle progression (Cyclin D1, Cyclin E1 and PCNA) were down-regulated in USP42-suppressed cells. Moreover, inhibition of USP42 in GC cells impaired cell invasion via affecting the expression of matrix metalloproteinases (MMPs) and epithelial-mesenchymal transition (EMT) regulators. In conclusion, USP42 overexpression could be a potential prognostic marker for GC, regulate the survival and invasive properties of GC, and may represent a novel therapeutic molecular target for this tumor.
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PMID:Overexpression and Biological Function of Ubiquitin-Specific Protease 42 in Gastric Cancer. 2703 Sep 89

The human genome contains six genes coding for proteins validated in vitro as specific activators of the small GTPases "Ras-related protein Ral-A" and "Ras-related protein Ral-B", generically named Ral-guanine nucleotide exchange factors (RalGEF). Ral proteins are important contributors to Ras oncogenic signaling, and RAS oncogenes are important in human Non-Small Cell Lung Carcinoma (NSCLC). Therefore in this work, RalGEF contribution to oncogenic and non-oncogenic features of human NSCLC cell lines, as anchorage-dependent and independent growth, cell survival, and proliferation, was investigated. Among all human RalGEF, silencing of RGL1 and RALGPS1 had no detectable effect. However, silencing of either RGL2, RGL3, RALGDS or, to a larger extent, RALGPS2 inhibited cell population growth in anchorage dependent and independent conditions (up to 90 and 80%, respectively). RALGPS2 silencing also caused an increase in the number of apoptotic cells, up to 45% of the cell population in transformed bronchial BZR cells. In H1299 and A549, two NSCLC cell lines, RALGPS2 silencing caused an arrest of cells in the G0/G1-phase of cell cycle. Furthermore, it was associated with the modulation of important cell cycle regulators: the E3 Ubiquitin Protein Ligase S-phase kinase-associated protein 2 (Skp2) was strongly down-regulated (both at mRNA and protein levels), and its targets, the cell cycle inhibitors p27 and p21, were up-regulated. These molecular effects were not mimicked by silencing RALA, RALB, or both. However, RALB silencing caused a modest inhibition of cell cycle progression, which in H1299 cells was associated with Cyclin D1 regulation. In conclusion, RALGPS2 is implicated in the control of cell cycle progression and survival in the in vitro growth of NSCLC cell lines. This function is largely independent of Ral GTPases and associated with modulation of Skp2, p27 and p21 cell cycle regulators.
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PMID:RalGPS2 Is Essential for Survival and Cell Cycle Progression of Lung Cancer Cells Independently of Its Established Substrates Ral GTPases. 2714 77

Ubiquitin-specific protease 44 (USP44) has been reported as a tumor suppressor or promoter in some tumors, but its function in non-small cell lung cancer (NSCLC) is still unclear. In this study, USP44 was found significantly downregulated in both of NSCLC tissues and cell lines, and low expression of USP44 predicted a poor prognosis for NSCLC patients. Overexpression of USP44 markedly downregulated the expression levels of Cyclin D1 and CDK4, but upregulated p53 expression, as a result of which, suppressing the cell growth of NSCLC cells. Further studies indicated that overexpression of USP44 significantly inhibited the phosphorylation of AKT, and its down-stream signals, including mTOR and P70S6K. Moreover, overexpression of USP44 increased PTEN protein but not its mRNA levels, which suggested that USP44 inhibited AKT signaling by stabilizing PTEN in NSCLC cells. In conclusion, we demonstrated that USP44 showed prior evidence of a tumor suppressive function in NSCLC cells, and inhibited NSCLC cell growth by suppressing AKT signaling, suggesting that USP44 could be as a novel target for NSCLC therapy.
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PMID:Ubiquitin-specific protease 44 inhibits cell growth by suppressing AKT signaling in non-small cell lung cancer. 3119 57