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 familial cylindromatosis tumour suppressor CYLD contains three cytoskeleton-associated protein glycine-rich (CAP-Gly) domains and a deubiquitinase domain. The tumour-suppressing function of CYLD has been attributed to its deubiquitinase domain, which removes lysine-63-linked polyubiquitin chains from target proteins, leading to the inhibition of cell survival and proliferation. In this study, we have detected an interaction of CYLD with the mitotic kinase Aurora-B. The interaction is mediated by the third CAP-Gly domain of CYLD and results in suppression of Aurora-B activity. Mechanistic studies reveal that the inhibition of Aurora-B activity by CYLD is independent of its deubiquitinase activity. Instead, CYLD interacts with protein phosphatase 2A (PP2A) and promotes the ability of PP2A to bind and dephosphorylate Aurora-B at threonine-232. Cylindromatosis-associated truncating mutations of CYLD abolish its interaction with PP2A, its enhancing effect on the PP2A/Aurora-B interaction, and its inhibitory effect on Aurora-B activity. These findings uncover Aurora-B and PP2A as novel binding partners of CYLD and suggest that CYLD negatively regulates Aurora-B activity through acting on the PP2A axis.
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PMID:Tumour suppressor CYLD is a negative regulator of the mitotic kinase Aurora-B. 2059 89

Oral cancer is a common cancer of the head and neck. Oral squamous cell carcinoma (OSCC) represents almost 90% of the total cases of head and neck cancer. Ubiquitin-specific protease 22 (USP22) is a deubiquitinating hydrolase, and it is highly expressed in various types of cancer, which also typically have a poor prognosis. Aurora-B and Survivin, which belong to the chromosomal passenger complex, are also highly expressed in a number of types of cancer. In the present study, USP22 expression and its associations with Aurora-B and Survivin, and the clinicopathological features in OSCC were explored. USP22 is highly expressed in OSCC. Overexpression of USP22 is associated with lymph node metastasis and histological grade (P<0.01). Additionally, the expression of USP22 was positively associated with Aurora-B (P<0.01), Survivin (P<0.01), and Ki-67 (P<0.01). Furthermore, USP22 small interfering RNA inhibited cell growth and reduced the expression levels of Aurora-B, Survivin and Cyclin B, together with the upregulation of cyclin-dependent kinase inhibitor 1A (p21). These data suggest that USP22, Aurora-B and Survivin promote the OSCC development and may represent novel targets for OSCC diagnosis and treatment in the future.
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PMID:Expression of USP22 and the chromosomal passenger complex is an indicator of malignant progression in oral squamous cell carcinoma. 3067 71

Endometrial carcinoma(EC) is the most common cancer of female reproductive system, thus requiring for new effective biomarkers which could predict the onset of EC and poor prognosis. Our study integrated two GEO datasets(i.e.GSE63678, GSE17025) and TCGA(The Cancer Genome Atlas ) UCEC data to screen out 344 common differentially expressed genes(DEGs), which were further analyzed by GO(gene ontology) functions and KEGG(Kyoto Encyclopedia of Gene and Genome) pathways. KEGG analysis results showed these DEGs were mainly enriched in cell cycle, oocyte meiosis, cellular senescence, carbon metabolism and p53 signaling pathway. Top 20 hub genes with higher degree were selected from PPI(protein-protein interaction) network and 15 of them were associated with the prognosis of EC, that is, CCNB2, CDC20, BUB1B, UBE2C, AURKB, FOXM1, NCAPG, RRM2, TPX2, DLGAP5, CDCA8, CDC45, MKI67, BUB1, KIF2C. UBE2C(Ubiquitin Conjugating Enzyme E2 C) was chosen for further validation in TCGA cohort on mRNA level and in our patient samples on protein level by immunohistochemistry. UBE2C was significantly highly expressed in endometrial carcinoma, and its expression level was associated with advanced FIGO staging and poor prognosis. Cox risk model demonstrated high UBE2C expression was an independent risk factor. Somatic mutations, elevated copy number, DNA hypomethylation all contributed to its overexpression. Therefore, by combination of bioinformatics and experiment, our study provided a unique insight into the pathogenesis and molecular mechanisms underlying EC and discovered new biomarkers for early diagnosis and prognostic prediction. UBE2C could serve as a potential marker to predict poor prognosis and as a therapeutic target.
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PMID:Combining Bioinformatics and Experiments to Identify and Verify Key Genes with Prognostic Values in Endometrial Carcinoma. 3194 95