Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.53 (sialidase)
 2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In mammalian cells, four types of sialidase have been described and found to behave in different ways during carcinogenesis. We previously demonstrated that a human sialidase associated with plasma membranes (NEU3) is up-regulated in human colon cancer and is involved in suppression of apoptosis. Here we document altered expression of another human sialidase, the recently identified NEU4, and evidence of its influence on the malignant phenotype in colon cancers. Human colon mucosa was relatively rich in NEU4, which has been observed to possess short and long isoforms, but hardly contained the latter form. In clear contrast to the NEU3 case, the levels of mRNA for this sialidase were found by quantitative RT-PCR to be markedly decreased in colon cancers. In cultured human colon cancer cells, the enzyme was up-regulated in the early stage of apoptosis induced by either the death ligand TRAIL or serum-depletion, and transfection of NEU4 resulted in acceleration of apoptosis and in decreased invasion and motility. The siRNA-mediated NEU4 targeting, on the other hand, caused a significant inhibition of apoptosis and promotion of invasion and motility. Lectin blot analyses revealed that desialylated forms of nearly 100 kDa glycoproteins were prominently increased with PNA in NEU4 transfectants, whereas only slight changes in glycolipids were detected as assessed by thin layer chromatography. These results suggest that NEU4 plays important roles for maintenance of normal mucosa mostly through desialylation of glycoproteins and that down-regulation may contribute to invasive properties of colon cancers.
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PMID:Down-regulation of sialidase NEU4 may contribute to invasive properties of human colon cancers. 1727 19

Protein modifications of death receptor pathways play a central role in the regulation of apoptosis. It has been demonstrated that O-glycosylation of TRAIL-receptor (R) is essential for sensitivity and resistance towards TRAIL-mediated apoptosis. In this study we ask whether and how glycosylation of CD95 (Fas/APO-1), another death receptor, influences DISC formation and procaspase-8 activation at the CD95 DISC and thereby the onset of apoptosis. We concentrated on N-glycostructure since O-glycosylation of CD95 was not found. We applied different approaches to analyze the role of CD95 N-glycosylation on the signal transduction: in silico modeling of CD95 DISC, generation of CD95 glycosylation mutants (at N136 and N118), modulation of N-glycosylation by deoxymannojirimycin (DMM) and sialidase from Vibrio cholerae (VCN). We demonstrate that N-deglycosylation of CD95 does not block DISC formation and results only in the reduction of the procaspase-8 activation at the DISC. These findings are important for the better understanding of CD95 apoptosis regulation and reveal differences between apoptotic signaling pathways of the TRAIL and CD95 systems.
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PMID:Modulation of the CD95-induced apoptosis: the role of CD95 N-glycosylation. 2162 44