Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deltex-3-like (DTX3L), an E3 ligase, is a member of the Deltex (DTX) family and is also called B-lymphoma and BAL-associated protein (BBAP). Previously, we established RFP/RET-transgenic mice, in which systemic hyperpigmented skin, benign melanocytic tumor(s) and melanoma(s) develop stepwise. Here we showed that levels of Dtx3l/DTX3L in spontaneous melanoma in RFP/RET-transgenic mice and human melanoma cell lines were significantly higher than those in benign melanocytic cells and primarily cultured normal human epithelial melanocytes, respectively. Immunohistochemical analysis of human tissues showed that more than 80% of the melanomas highly expressed DTX3L. Activity of FAK/PI3K/AKT signaling, but not that of MEK/ERK signaling, was decreased in Dtx3l/DTX3L-depleted murine and human melanoma cells. In summary, we demonstrated not only increased DTX3L level in melanoma cells but also DTX3L-mediated regulation of invasion and metastasis in melanoma through FAK/PI3K/AKT but not MEK/ERK signaling. Our analysis in human BRAFV600E inhibitor-resistant melanoma cells showed about 80% decreased invasion in the DTX3L-depleted cells compared to that in the DTX3L-intact cells. Thus, DTX3L is clinically a potential therapeutic target as well as a potential biomarker for melanoma.
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PMID:Deltex-3-like (DTX3L) stimulates metastasis of melanoma through FAK/PI3K/AKT but not MEK/ERK pathway. 2603 50

MicroRNA signatures of BAL cells and alveolar macrophages are currently lacking in IPF. Here we sought to investigate the expression of fibrosis-related microRNAs in the cellular component of the BAL in IPF. We thus focused on microRNAs previously associated with fibrosis (miR-29a, miR-29b, miR-29c, let-7d, and miR-21) and rapid IPF progression (miR-185, miR-210, miR-302c-3p miR-376c and miR-423-5p). Among the tested microRNAs miR-29a and miR-185 were found significantly downregulated in IPF while miR-302c-3p and miR-376c were not expressed by BAL cells. Importantly, the downregulation of miR-29a inversely correlated with the significantly increased levels of COL1A1 mRNA in IPF BAL cells. Collagen 1 a was found mainly overexpressed in alveolar macrophages and not other cell types of the BAL by immunofluorescence. In view of the downregulation of miR-185, we tested the response of THP-1 macrophages to profibrotic cytokine TGFb and observed the downregulation of miR-185. Conversely, proinflammatory stimulation lead to miR-185 upregulation. Upon examination of the mRNA levels of known miR-185 targets AKT1, DNMT1 and HMGA2, no significant correlations were observed in the BAL cells. However, increased levels of total AKT and AKTser473 phosphorylation were observed in the IPF BAL cells. Furthermore, miR-185 inhibition in THP-1 macrophages resulted in significant increase of AKTser473 phosphorylation. Our study highlights the importance of BAL microRNA signatures in IPF and identifies significant differences in miR-185/AKT and miR-29a/collagen axes in the BAL cells of IPF patients.
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PMID:MiR-185/AKT and miR-29a/collagen 1a pathways are activated in IPF BAL cells. 2776 60