The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

NBL1  -  neuroblastoma 1, DAN family BMP antagonist

Homo sapiens

Synonyms: D1S1733E, DAN, DAN domain family member 1, DAND1, NB, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of NBL1


Psychiatry related information on NBL1

  • Ten DAN+ exhibited a mean lowest oxygen saturation < 90% during REM sleep [6].
  • In the case of I-3F8 for pediatric NB therapy, the demonstrated variability in effective half-time suggests the need for patient-specific tracer dosimetry for both optimization of treatment and radiation safety precaution decision-making [7].

High impact information on NBL1

  • Thus, cell death susceptibility correlates with NB recruitment of NB proteins [8].
  • Neuroblastoma (NB) is the most common extracranial solid neoplasm of infancy and is associated with very poor prognosis in patients with advanced disease [9].
  • We have found highly predictable patterns of protooncogene expression in cell lines and tumor tissue of neuroblastoma (NB), a tumor of the peripheral nervous system (PNS) [10].
  • PHOX2B, therefore, stands as the first gene for which germline mutations predispose to NB [5].
  • We propose that rapid inhibition of cdks by RA in NB leads to early cell cycle arrest, prevents neuronal differentiation, and results in a senescence-like state [11].

Chemical compound and disease context of NBL1


Biological context of NBL1

  • Human DAN gene mapped to chromosome 1p36.11-p36.13, which is well known to show highly significant linkage with the genesis and/or progression of human neuroblastoma [1].
  • Collectively, we propose that human DAN gene is a possible candidate for a tumor suppressor gene of human neuroblastoma [1].
  • To assess the involvement of DAN gene with human neoplasms, we have isolated human DAN counterpart from a normal lung cDNA library by using rat DAN cDNA as a probe, and determined its chromosomal location [1].
  • Because the glycosylation process is involved in the progression of primary tumor to metastatic disease, we investigated whether the most strongly up-regulated gene, GALNT13, might be a marker of bone marrow involvement in stage 4 NB patients [2].
  • A product of DAN, a novel candidate tumour suppressor gene, is secreted into culture medium and suppresses DNA synthesis [3].

Anatomical context of NBL1

  • The expression of DAN gene (previously designated as N03 gene) is significantly reduced in a variety of transformed rat fibroblasts, including v-src- (SR-3Y1), SV40- and v-mos-transformed 3Y1 cells, compared with that in parental 3Y1 cells [1].
  • BACKGROUND: To identify new molecular markers of bone marrow dissemination in human neuroblastoma (NB), we studied the transcriptome profiles of malignant neuroblasts established from the human MYCN-amplified IGR-N-91 model [2].
  • p73-dependent expression of DAN during cisplatin-induced cell death and osteoblast differentiation [16].
  • A relationship to neuroblastoma (NB), a pediatric tumor of the sympathetic nervous system, is based on morphologic similarities and the expression of similar neural antigens [17].
  • Spectrophotometric studies showed that PIH could chelate Ga, and it can be suggested that, like the PIH-Fe complex that donates Fe to reticulocytes (Ponka et al, Biochim Biophys Acta 718:151, 1982), the PIH-Ga complex may efficiently bestow Ga to NB cells [18].

Associations of NBL1 with chemical compounds

  • Additionally, the expression of DAN was increased in response to cisplatin-induced cell death of neuroblastoma SH-SY5Y cells [16].
  • Here we analyze the mechanistic basis for the different effects of RA in the two NB subclones [11].
  • Moreover, retinoic acid (RA) had different effects on the two NB cell lines: on LAN-5 cells it acts as a differentiation-promoting agent, while on GI-LI-N cells it has an antiproliferative effect, driving them to apoptosis [15].
  • Marked induction of bcl-2 in NB cells followed RA-induced differentiation, whereas in cell lines failing to differentiate, bcl-2 was not detected [14].
  • Two SH-SY5Y NB cell lines (TB3 and TB8) expressing TrkB under the control of a tetracycline (Tet)-repressible promoter element were generated, and used to assess apoptosis resulting from treatment with cisplatin, doxorubicin, etoposide, and vinblastine [19].

Regulatory relationships of NBL1


Other interactions of NBL1

  • The deletion experiment revealed that the N-terminal region (amino acid residues 1-80) of DAN was required for the interaction with BAT3 [21].
  • Recently, we have identified a new protein (DA41) which can associate with candidate tumor-suppressor DAN protein [22].
  • Northern blot analysis revealed that DAN mRNA was detected in OS-KH and RMS-NK cells, but was not detectable in SAOS-2, NOS-1, and ASPS-KY cells [23].
  • In the present study, we generated a novel monoclonal antibody (NBL-1) to RET, a receptor tyrosine kinase expressed in both neuroblastoma cells and cells present in substantia nigra, a responsive locus of Parkinson's disease [24].

Analytical, diagnostic and therapeutic context of NBL1

  • Southern blot analysis on tumor DNA from 26 patients with neuroblastoma has detected three patients showing genomic rearrangement or deletion within or closely linked to the DAN gene locus [1].
  • Current therapeutic regimens of advanced NB which combine surgical resection with radiation therapy and/or chemotherapy brought some improvements, but in a significant number of patients, a cure remains elusive [9].
  • The antigen was expressed in vivo as detected by immunohistochemistry in both the tumor of a NB patient and NB tumors established in nude rats from human NB cell lines [4].
  • Further analyses revealed that a 260-kDa protein was recognized by natural IgM of cytotoxic sera in Western blots of NB cell extracts [4].
  • Typically, NB cells differentiate along the neuronal lineage, but quiescent, "flat" cell types frequently have been described after treatment with differentiating agents [11].


  1. Identification of human DAN gene, mapping to the putative neuroblastoma tumor suppressor locus. Enomoto, H., Ozaki, T., Takahashi, E., Nomura, N., Tabata, S., Takahashi, H., Ohnuma, N., Tanabe, M., Iwai, J., Yoshida, H. Oncogene (1994) [Pubmed]
  2. ppGalNAc-T13: a new molecular marker of bone marrow involvement in neuroblastoma. Berois, N., Blanc, E., Ripoche, H., Mergui, X., Trajtenberg, F., Cantais, S., Barrois, M., Dessen, P., Kågedal, B., Bénard, J., Osinaga, E., Raguénez, G. Clin. Chem. (2006) [Pubmed]
  3. A product of DAN, a novel candidate tumour suppressor gene, is secreted into culture medium and suppresses DNA synthesis. Nakamura, Y., Ozaki, T., Nakagawara, A., Sakiyama, S. Eur. J. Cancer (1997) [Pubmed]
  4. Normal human serum contains a natural IgM antibody cytotoxic for human neuroblastoma cells. Ollert, M.W., David, K., Schmitt, C., Hauenschild, A., Bredehorst, R., Erttmann, R., Vogel, C.W. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  5. Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma. Trochet, D., Bourdeaut, F., Janoueix-Lerosey, I., Deville, A., de Pontual, L., Schleiermacher, G., Coze, C., Philip, N., Frébourg, T., Munnich, A., Lyonnet, S., Delattre, O., Amiel, J. Am. J. Hum. Genet. (2004) [Pubmed]
  6. Sleep-disordered breathing in nonobese diabetic subjects with autonomic neuropathy. Bottini, P., Dottorini, M.L., Cristina Cordoni, M., Casucci, G., Tantucci, C. Eur. Respir. J. (2003) [Pubmed]
  7. Whole-body clearance kinetics and external dosimetry of 131I-3F8 monoclonal antibody for radioimmunotherapy of neuroblastoma. Dauer, L.T., St Germain, J., Williamson, M.J., Zanzonico, P., Modak, S., Cheung, N.K., Divgi, C. Health physics (2007) [Pubmed]
  8. PML induces a novel caspase-independent death process. Quignon, F., De Bels, F., Koken, M., Feunteun, J., Ameisen, J.C., de Thé, H. Nat. Genet. (1998) [Pubmed]
  9. Growth arrest of solid human neuroblastoma xenografts in nude rats by natural IgM from healthy humans. David, K., Ollert, M.W., Juhl, H., Vollmert, C., Erttmann, R., Vogel, C.W., Bredehorst, R. Nat. Med. (1996) [Pubmed]
  10. Differential protooncogene expression characterizes histopathologically indistinguishable tumors of the peripheral nervous system. Thiele, C.J., McKeon, C., Triche, T.J., Ross, R.A., Reynolds, C.P., Israel, M.A. J. Clin. Invest. (1987) [Pubmed]
  11. Distinct mechanisms of cell cycle arrest control the decision between differentiation and senescence in human neuroblastoma cells. Wainwright, L.J., Lasorella, A., Iavarone, A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  12. Purification and partial amino acid sequence of proteins from human epidermal keratinocyte conditioned medium. Ahmed, A., Kandola, P., Ziada, G., Parenteau, N. J. Protein Chem. (2001) [Pubmed]
  13. Signals transduced via insulin-like growth factor I receptor (IGF(R)) mediate resistance to retinoic acid-induced cell growth arrest in a human neuroblastoma cell line. Matsumoto, K., Lucarelli, E., Minniti, C., Gaetano, C., Thiele, C.J. Cell Death Differ. (1994) [Pubmed]
  14. Differentiation of neuroblastoma enhances Bcl-2 expression and induces alterations of apoptosis and drug resistance. Lasorella, A., Iavarone, A., Israel, M.A. Cancer Res. (1995) [Pubmed]
  15. Integrin up-regulation as marker of neuroblastoma cell differentiation: correlation with neurite extension. Rozzo, C., Chiesa, V., Ponzoni, M. Cell Death Differ. (1997) [Pubmed]
  16. p73-dependent expression of DAN during cisplatin-induced cell death and osteoblast differentiation. Shinbo, J., Ozaki, T., Nakagawa, T., Watanabe, K., Nakamura, Y., Yamazaki, M., Moriya, H., Nakagawara, A., Sakiyama, S. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  17. Olfactory neuroblastoma is a peripheral primitive neuroectodermal tumor related to Ewing sarcoma. Sorensen, P.H., Wu, J.K., Berean, K.W., Lim, J.F., Donn, W., Frierson, H.F., Reynolds, C.P., López-Terrada, D., Triche, T.J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  18. The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents. Richardson, D.R., Tran, E.H., Ponka, P. Blood (1995) [Pubmed]
  19. Brain-derived neurotrophic factor activation of TrkB protects neuroblastoma cells from chemotherapy-induced apoptosis via phosphatidylinositol 3'-kinase pathway. Jaboin, J., Kim, C.J., Kaplan, D.R., Thiele, C.J. Cancer Res. (2002) [Pubmed]
  20. Gremlin: an example of the re-emergence of developmental programmes in diabetic nephropathy. Lappin, D.W., McMahon, R., Murphy, M., Brady, H.R. Nephrol. Dial. Transplant. (2002) [Pubmed]
  21. Cloning and characterization of rat BAT3 cDNA. Ozaki, T., Hanaoka, E., Naka, M., Nakagawara, A., Sakiyama, S. DNA Cell Biol. (1999) [Pubmed]
  22. Interaction of DA41, a DAN-binding protein, with the epidermal growth factor-like protein, S(1-5). Ozaki, T., Kondo, K., Nakamura, Y., Ichimiya, S., Nakagawara, A., Sakiyama, S. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  23. Overexpression of DAN causes a growth suppression in p53-deficient SAOS-2 cells. Hanaoka, E., Ozaki, T., Nakamura, Y., Moriya, H., Nakagawara, A., Sakiyama, S. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  24. Improved gene transfer to neuroblastoma cells by a monoclonal antibody targeting RET, a receptor tyrosine kinase. Yano, L., Shimura, M., Taniguchi, M., Hayashi, Y., Suzuki, T., Hatake, K., Takaku, F., Ishizaka, Y. Hum. Gene Ther. (2000) [Pubmed]
WikiGenes - Universities