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BCAR3  -  breast cancer anti-estrogen resistance 3

Homo sapiens

Synonyms: Breast cancer anti-estrogen resistance protein 3, NSP2, Novel SH2-containing protein 2, SH2 domain-containing protein 3B, SH2D3B, ...
 
 
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Disease relevance of BCAR3

  • Breast cancer oestrogen independence mediated by BCAR1 or BCAR3 genes is transmitted through mechanisms distinct from the oestrogen receptor signalling pathway or the epidermal growth factor receptor signalling pathway [1].
  • The Chinese adult diarrhea rotavirus (ADRV) and the Indian CAL strains of human group B rotaviruses were reported to be conserved in genes encoding structural proteins but divergent in NSP2 and NSP3 genes, raising the questions about the origin and the evolution of these strains [2].
  • Here, we identify SARS coronavirus amino-terminal replicase products nsp1, nsp2, and nsp3 and describe trans-cleavage assays that characterize the protease activity required to generate these products [3].
  • Expression of two bovine rotavirus non-structural proteins (NSP2, NSP3) in the baculovirus system and production of monoclonal antibodies directed against the expressed proteins [4].
  • In the severe acute respiratory syndrome (SARS) associated human corona virus, the spike glycoprotein and nsps (nsp2, nsp5, nsp6 and nsp7) were identified as having adhesin-like characteristics [5].
 

High impact information on BCAR3

  • Identification of BCAR3 by a random search for genes involved in antiestrogen resistance of human breast cancer cells [6].
  • Transfer of this locus by cell fusion or transfection of the BCAR3 cDNA to ZR75-1 and MCF-7 cells induces antiestrogen resistance [6].
  • BCAR3 represents a putative SH2 domain-containing protein and is partly homologous to the cell division cycle protein CDC48 [6].
  • Here we demonstrate that both R-Ras and BCAR3, a regulator of R-Ras activity that has been implicated in breast cancer, regulate the level of IRS-1 protein in estrogen-dependent MCF-7 and ZR75 breast cancer cells [7].
  • Overexpression of either of the human homologues of AND-34 and p130Cas, BCAR3 and BCAR1, respectively, has been reported to induce resistance to antiestrogens in breast cancer cell lines [8].
 

Biological context of BCAR3

 

Anatomical context of BCAR3

 

Associations of BCAR3 with chemical compounds

  • Transient transfection of BCAR3 in estrogen-dependent MCF7 cells induced activation of luciferase constructs containing the proximal 1745 or 163 bp but not 66 bp of the cyclin D1 promoter [8].
  • Working in concert with Pyk2, adaptor protein CrkII and a recently discovered guanidine exchange factor for certain small GTPases BCAR3 can be involved in ET-1 signaling in the kidney [9].
  • Then the recombinant eukaryotic expression vector pCI-neo/nsp2 was transfected into COS-7 cells using lipofectin reagent to express the nsp2 protein [11].
 

Other interactions of BCAR3

  • Both BCAR1 and BCAR3 regulate discrete sets of genes in these ZR-75-1-derived cells, indicating that the proliferation signalling proceeds along distinct pathways [1].
  • We found that the PLpro domain is sufficient for processing the predicted nsp1/2 and nsp2/3 sites [3].
  • In contrast, processing at the nsp2/3 site is less efficient, since a approximately 300-kDa intermediate (NSP2-3) is detected, but ultimately nsp2 (p71) and nsp3 (p213) are generated [3].
 

Analytical, diagnostic and therapeutic context of BCAR3

References

  1. Breast cancer oestrogen independence mediated by BCAR1 or BCAR3 genes is transmitted through mechanisms distinct from the oestrogen receptor signalling pathway or the epidermal growth factor receptor signalling pathway. Dorssers, L.C., van Agthoven, T., Brinkman, A., Veldscholte, J., Smid, M., Dechering, K.J. Breast Cancer Res. (2005) [Pubmed]
  2. The evolution of human group B rotaviruses: correction and an update. Jiang, B., Wang, Y., Glass, R.I., Fang, Z.Y. J. Clin. Virol. (2005) [Pubmed]
  3. Identification of severe acute respiratory syndrome coronavirus replicase products and characterization of papain-like protease activity. Harcourt, B.H., Jukneliene, D., Kanjanahaluethai, A., Bechill, J., Severson, K.M., Smith, C.M., Rota, P.A., Baker, S.C. J. Virol. (2004) [Pubmed]
  4. Expression of two bovine rotavirus non-structural proteins (NSP2, NSP3) in the baculovirus system and production of monoclonal antibodies directed against the expressed proteins. Aponte, C., Mattion, N.M., Estes, M.K., Charpilienne, A., Cohen, J. Arch. Virol. (1993) [Pubmed]
  5. SPAAN: a software program for prediction of adhesins and adhesin-like proteins using neural networks. Sachdeva, G., Kumar, K., Jain, P., Ramachandran, S. Bioinformatics (2005) [Pubmed]
  6. Identification of BCAR3 by a random search for genes involved in antiestrogen resistance of human breast cancer cells. van Agthoven, T., van Agthoven, T.L., Dekker, A., van der Spek, P.J., Vreede, L., Dorssers, L.C. EMBO J. (1998) [Pubmed]
  7. The R-Ras GTPase mediates cross talk between estrogen and insulin signaling in breast cancer cells. Yu, Y., Hao, Y., Feig, L.A. Mol. Cell. Biol. (2006) [Pubmed]
  8. AND-34/BCAR3, a GDP exchange factor whose overexpression confers antiestrogen resistance, activates Rac, PAK1, and the cyclin D1 promoter. Cai, D., Iyer, A., Felekkis, K.N., Near, R.I., Luo, Z., Chernoff, J., Albanese, C., Pestell, R.G., Lerner, A. Cancer Res. (2003) [Pubmed]
  9. CrkII associates with BCAR3 in response to endothelin-1 in human glomerular mesangial cells. Rufanova, V.A., Sorokin, A. Exp. Biol. Med. (Maywood) (2006) [Pubmed]
  10. Identification and characterization of human FNBP1L gene in silico. Katoh, M., Katoh, M. Int. J. Mol. Med. (2004) [Pubmed]
  11. Variation analysis of the severe acute respiratory syndrome coronavirus putative non-structural protein 2 gene and construction of three-dimensional model. Lu, J.H., Zhang, D.M., Wang, G.L., Guo, Z.M., Zhang, C.H., Tan, B.Y., Ouyang, L.P., Lin, L., Liu, Y.M., Chen, W.Q., Ling, W.H., Yu, X.B., Zhong, N.S. Chin. Med. J. (2005) [Pubmed]
  12. CD4(+) T cell frequencies and Th1/Th2 cytokine patterns expressed in the acute and memory response to respiratory syncytial virus I-E(d)-restricted peptides. Tripp, R.A., Hou, S., Etchart, N., Prinz, A., Moore, D., Winter, J., Anderson, L.J. Cell. Immunol. (2001) [Pubmed]
 
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