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Gene Review

Nbl1  -  neuroblastoma, suppression of...

Mus musculus

Synonyms: D4H1S1733E, DAN, Dan, Dana, N03, ...
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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


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


  1. Protease activity associated with loss of adhesiveness in mouse teratocarcinoma. Meyer, J.T., Thompson, P.M., Behringer, R., Steiner, R.C., Saxton, W.M., Oppenheimer, S.B. Exp. Cell Res. (1983) [Pubmed]
  2. Reduced inflammatory pain in mice deficient in the differential screening-selected gene aberrative in neuroblastoma. Ohtori, S., Isogai, E., Hasue, F., Ozaki, T., Nakamura, Y., Nakagawara, A., Koseki, H., Yuasa, S., Hanaoka, E., Shinbo, J., Yamamoto, T., Chiba, H., Yamazaki, M., Moriya, H., Sakiyama, S. Mol. Cell. Neurosci. (2004) [Pubmed]
  3. Variants of bcl-2 specific siRNA for silencing antiapoptotic bcl-2 in pancreatic cancer. Ocker, M., Neureiter, D., Lueders, M., Zopf, S., Ganslmayer, M., Hahn, E.G., Herold, C., Schuppan, D. Gut (2005) [Pubmed]
  4. Insulin activates Stat3 independently of p21ras-ERK and PI-3K signal transduction. Coffer, P.J., van Puijenbroek, A., Burgering, B.M., Klop-de Jonge, M., Koenderman, L., Bos, J.L., Kruijer, W. Oncogene (1997) [Pubmed]
  5. A mouse cerberus/Dan-related gene family. Pearce, J.J., Penny, G., Rossant, J. Dev. Biol. (1999) [Pubmed]
  6. DAN is a secreted glycoprotein related to Xenopus cerberus. Stanley, E., Biben, C., Kotecha, S., Fabri, L., Tajbakhsh, S., Wang, C.C., Hatzistavrou, T., Roberts, B., Drinkwater, C., Lah, M., Buckingham, M., Hilton, D., Nash, A., Mohun, T., Harvey, R.P. Mech. Dev. (1998) [Pubmed]
  7. Cloning and expression analysis of the chick DAN gene, an antagonist of the BMP family of growth factors. Gerlach-Bank, L.M., Ellis, A.D., Noonen, B., Barald, K.F. Dev. Dyn. (2002) [Pubmed]
  8. Cloning of mouse DAN cDNA and its down-regulation in transformed cells. Ozaki, T., Ma, J., Takenaga, K., Sakiyama, S. Jpn. J. Cancer Res. (1996) [Pubmed]
  9. Chromosome mapping of the mouse and rat homologs of the human DAN gene, D1S1733E. Matsuda, Y., Ozaki, T., Enomoto, H., Saito, T., Sakiyama, S. Mamm. Genome (1996) [Pubmed]
  10. DAN directs endolymphatic sac and duct outgrowth in the avian inner ear. Gerlach-Bank, L.M., Cleveland, A.R., Barald, K.F. Dev. Dyn. (2004) [Pubmed]
  11. Gastrin/cholecystokinin-like immunoreactive peptides in the Dungeness crab, Cancer magister (Dana): immunochemical and biological characterization. Larson, B.A., Vigna, S.R. Regul. Pept. (1983) [Pubmed]
  12. Reproductive defects in the male diabetic athymic nude mouse. Zeidler, A., Shargill, N.S., Meehan, W.P., Warren, D.W. Biochem. Med. Metab. Biol. (1987) [Pubmed]
  13. Interplay between bone morphogenetic proteins and cognate binding proteins in bone and cartilage development: noggin, chordin and DAN. Reddi, A.H. Arthritis Res. (2001) [Pubmed]
  14. Mutation and analysis of Dan, the founding member of the Dan family of transforming growth factor beta antagonists. Dionne, M.S., Skarnes, W.C., Harland, R.M. Mol. Cell. Biol. (2001) [Pubmed]
  15. Potentiation of 5-fluoro-2'-deoxyuridine antineoplastic activity by the uridine phosphorylase inhibitors benzylacyclouridine and benzyloxybenzylacyclouridine. Chu, M.Y., Naguib, F.N., Iltzsch, M.H., el Kouni, M.H., Chu, S.H., Cha, S., Calabresi, P. Cancer Res. (1984) [Pubmed]
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