Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Large-scale, genome-wide studies report that RNA binding proteins are altered in cancers, but it is unclear how these proteins control tumor progression. We found that the RNA-editing protein ADAR (adenosine deaminase acting on double-stranded RNA) acted as a facilitator of lung adenocarcinoma (LUAD) progression through its ability to stabilize transcripts encoding focal adhesion kinase (FAK). In samples from 802 stage I LUAD patients, increased abundance of ADAR at both the mRNA and protein level correlated with tumor recurrence. Knocking down ADAR in LUAD cells suppressed their mesenchymal properties, migration, and invasion in culture. Analysis of gene expression patterns in LUAD cells identified ADAR-associated enrichment of a subset of genes involved in cell migration pathways; among these, FAK is the most notable gene whose expression was increased in the presence of ADAR. Molecular analyses revealed that ADAR posttranscriptionally increased FAK protein abundance by binding to the FAK transcript and editing a specific intronic site that resulted in the increased stabilization of FAK mRNA. Pharmacological inhibition of FAK blocked ADAR-induced invasiveness of LUAD cells, suggesting a potential therapeutic application for LUAD that has a high abundance of ADAR.
 ...
PMID:The RNA-editing enzyme ADAR promotes lung adenocarcinoma migration and invasion by stabilizing FAK. 2892 39

Skeletal development throughout the embryonic and postnatal phases is a dynamic process, based on bone remodeling and the balance between the activities of osteoclasts and osteoblasts modulating skeletal homeostasis. The Notch signaling pathway is a regulator of several developmental processes, and plays a crucial role in the development of the human skeleton by regulating the proliferation and differentiation of skeletal cells. The Delta Like-1 (DLL1) gene plays an important role in Notch signaling. We propose that an identified alteration in DLL1 protein may affect the downstream signaling. In this article, we present for the first time two siblings with a mutation in the DLL1 gene, presenting with congenital vertebral malformation. Using variable in silico prediction tools, it was predicted that the variant was responsible for the development of disease. Quantitative reverse-transcription polymerase chain reaction (PCR) for the Notch signaling pathway, using samples obtained from patients, showed a significant alteration in the expression of various related genes. Specifically, the expression of neurogenic locus notch homolog protein 1, SNW domain-containing protein 1, disintegrin, and metalloproteinase domain-containing proteins 10 and 17, was upregulated. In contrast, the expression of HEY1, HEY2, adenosine deaminase (ADA), and mastermind-like-1 (MAML-1) was downregulated. Furthermore, in a phosphokinase array, four kinases were significantly changed in patients, namely, p27, JANK1/2/3, mitogen- and stress-activated protein kinases 1 and 2, and focal adhesion kinase. Our results suggest an implication of a DLL1 defect related to the Notch signaling pathway, at least in part, in the morphologic abnormality observed in these patients. A limitation of our study was the low number of patients and samples. Further studies in this area are warranted to decipher the link between a DLL1 defect and skeletal abnormality.
 ...
PMID:Delta Like-1 Gene Mutation: A Novel Cause of Congenital Vertebral Malformation. 3127 52