EC:2.7.11.24 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.24 (mitogen-activated protein kinase)
95,810 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The glycosaminoglycan hyaluronan (HA) modulates cell proliferation and migration, and it is involved in several human vascular pathologies including atherosclerosis and vascular restenosis. During intima layer thickening, HA increases dramatically in the neointima extracellular matrix. Aging is one of the major risk factors for the insurgence of vascular diseases, in which smooth muscle cells (SMCs) play a role by determining neointima formation through their migration and proliferation. Therefore, we established an in vitro aging model consisting of sequential passages of human aortic smooth muscle cells (AoSMCs). Comparing young and aged cells, we found that, during the aging process in vitro,HA synthesis significantly increases, as do HA synthetic enzymes (i.e. HAS2 and HAS3), the precursor synthetic enzyme (UDP-glucose dehydrogenase), and the HA receptor CD44. In aged cells, we also observed increased CD44 signaling that consisted of higher levels of phosphorylated MAP kinase ERK1/2. Further, aged AoSMCs migrated faster than young cells, and such migration could be modulated by HA, which alters the ERK1/2 phosphorylation. HA oligosaccharides of 6.8 kDa and an anti-CD44 blocking antibody prevented ERK1/2 phosphorylation and inhibited AoSMCs migration. These results indicate that, during aging, HA can modulate cell migration involving CD44-mediated signaling through ERK1/2. These data suggest that age-related HA accumulation could promote SMC migration and intima thickening during vascular neointima formation.
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PMID:Hyaluronan-CD44-ERK1/2 regulate human aortic smooth muscle cell motility during aging. 1807 44

The Epstein-Barr virus latent membrane protein 2A (LMP2A) is frequently detected in nasopharyngeal carcinoma (NPC), a tumour of high metastatic capacity. A recent microarray assay notes that expression of the UDP-glucose dehydrogenase (UGDH) gene, participating in glycosaminoglycan synthesis, shows high correlation with LMP2A levels in NPC biopsies. This study extends the finding and demonstrates that the UGDH transcript and protein quantities, the enzyme activity, and glycosaminoglycan contents increase in LMP2A overexpressed human embryonic kidney 293 (HEK293) cells. The luciferase reporter gene assay demarcates that a region from 630 to 486 bp upstream of the transcription start is critical for LMP2A-mediated gene expression. Moreover, a specificity protein 1 (Sp1) binding site mutation in this region reduces the LMP2A-responsive expression of the UGDH gene. Consistent with these findings, cell motility enhancement by LMP2A diminishes by treating the cells with Sp1-specific inhibitor and small interference RNA (siRNA). Using a signalling pathway-specific inhibitor, it is revealed that phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK), not c-Jun N-terminal kinase (JNK) and p38, participate in LMP2A-induced UGDH expression. This study provides a model for molecular mechanism participating in LMP2A-mediated UGDH gene activation.
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PMID:Epstein-Barr virus latent membrane protein 2A upregulates UDP-glucose dehydrogenase gene expression via ERK and PI3K/Akt pathway. 1871 19

More than 70% of patients with ovarian cancer are diagnosed in advanced stages. Therefore, it is urgent to identify a promising prognostic marker and understand the mechanism of ovarian cancer metastasis development. By using proteomics approaches, we found that UDP-glucose dehydrogenase (UGDH) was up-regulated in highly metastatic ovarian cancer TOV21G cells, characterized by high invasiveness (TOV21G^HI ), in comparison to its parental control. Previous reports demonstrated that UGDH is involved in cell migration, but its specific role in cancer metastasis remains unclear. By performing immunohistochemical staining with tissue microarray, we found overexpression of UGDH in ovarian cancer tissue, but not in normal adjacent tissue. Silencing using RNA interference (RNAi) was utilized to knockdown UGDH, which resulted in a significant decrease in metastatic ability in transwell migration, transwell invasion and wound healing assays. The knockdown of UGDH caused cell cycle arrest in the G₀ /G₁ phase and induced a massive decrease of tumour formation rate in vivo. Our data showed that UGDH-depletion led to the down-regulation of epithelial-mesenchymal transition (EMT)-related markers as well as MMP2, and inactivation of the ERK/MAPK pathway. In conclusion, we found that the up-regulation of UGDH is related to ovarian cancer metastasis and the deficiency of UGDH leads to the decrease of cell migration, cell invasion, wound healing and cell proliferation ability. Our findings reveal that UGDH can serve as a prognostic marker and that the inhibition of UGDH is a promising strategy for ovarian cancer treatment.
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PMID:Targeting UDP-glucose dehydrogenase inhibits ovarian cancer growth and metastasis. 3289 77