Disease relevance of Nbl1

• Ascites protease has a pH optimum of 2.0-3.0 and is inhibited by both DAN (diazoacetyl-DL-norleucine methyl ester) and Pepstatin A [1].

Psychiatry related information on Nbl1

• In the inflammatory pain model, thermal and mechanical pain thresholds in Dan-deficient mice were significantly higher than those of wild-type mice [2].

High impact information on Nbl1

• METHODS: siRNAs targeting two different regions in the bcl-2 gene were transfected to YAP C and DAN G pancreatic carcinoma cells and human foreskin fibroblasts [3].
• DAN binding of this complex is inhibited by pre-incubation with tyrosine, but not serine/threonine protein kinase inhibitors, whereas transcriptional activation is inhibited by both [4].
• Thermal and mechanical allodynia and Fos expression in the spinal dorsal horn evoked by inflammation and neuropathic pain were investigated using Dan-deficient mice [2].
• Differential screening-selected gene aberrative in neuroblastoma (Dan) protein is produced in small neurons of dorsal root ganglia [2].
• Dan is first seen in the head mesoderm of early head fold stage embryos and Drm is expressed in the lateral paraxial mesoderm at E8 [5].

Biological context of Nbl1

• During mouse embryogenesis, Dan was expressed from E8.5 in cranial mesenchyme and somites, then later in limb and facial mesenchyme [6].
• Overexpression of DAN suppresses the transformed phenotype and retards the cell's entry into S phase [7].
• Cloning of mouse DAN cDNA and its down-regulation in transformed cells [8].
• Genomic Southern blot hybridization indicated that DAN gene exists as a single copy in the mouse genome [8].
• Chromosome mapping of the mouse and rat homologs of the human DAN gene, D1S1733E [9].

Anatomical context of Nbl1

• Like cerberus and mCer-1, DAN-induced cement glands as well as markers of anterior neural tissue and endoderm in Xenopus animal cap assays, features of BMP signalling blockade [6].
• First isolated in a screen to identify genes down-regulated in transformed rat fibroblasts, DAN has subsequently been cloned in Xenopus, mouse, and human [7].
• In this study, the role of the BMP antagonist DAN in inner ear development was investigated [10].
• Unique to the DAN implantations, however, were effects on the developing endolymphatic duct and sac [10].
• This observation suggests that DAN may play different roles in chick and mouse otic and notochord development [7].

Associations of Nbl1 with chemical compounds

• Thus, DAN appears to be a secreted factor belonging to the cystine knot superfamily, and one of a growing number of antagonists acting to modulate BMP signalling during development [6].
• Using denatured bovine hemoglobin as a substrate, the low pH optimum and inhibition by DAN and Pepstatin A allow tentative identification of the enzyme as the carboxypeptidase Cathepsin D [1].
• Gastrin/cholecystokinin-like immunoreactive peptides in the Dungeness crab, Cancer magister (Dana): immunochemical and biological characterization [11].
• These results demonstrate that the impaired fertility observed in the DAN mouse may result from decreased testosterone production [12].

Other interactions of Nbl1

• BMP binding proteins, noggin, chordin and DAN, act as antagonists and determine the bioavailability of BMPs for binding to cognate receptors to elicit the biological response [13].

Analytical, diagnostic and therapeutic context of Nbl1

• Mice lacking Dan activity were generated by gene targeting and displayed subtle, background-dependent defects [14].
• Chick DAN expression generally corresponded to that of mouse DAN expression as shown by comparative in situ hybridization [7].
• Electroporation of DAN antisense morpholinos into the epithelium of stage 15-17 otocysts, blocking DAN protein synthesis, resulted in enlarged endolymphatic ducts and sacs as well as smaller semicircular canals in some cases [10].
• In antithymocyte serum-immunosuppressed mice bearing DAN, the mean tumor weight in animals treated with FdUrd (50 mg/kg/day for 2 days) was 11% less than that of untreated controls [15].

References