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Gene Review

Bcr  -  breakpoint cluster region

Mus musculus

Synonyms: 5133400C09Rik, AI561783, AI853148, Breakpoint cluster region protein, Kiaa3017, ...
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Disease relevance of Bcr


High impact information on Bcr

  • The biochemical target of CGP76030 in leukemia cells was Src kinases, not Bcr-Abl [4].
  • These results connect Bcr in vivo with the regulation of Rac-mediated superoxide production by the NADPH-oxidase system of leukocytes and suggest a link between Bcr function and the cell type affected in Ph-positive leukemia [6].
  • Cellular proliferation and tumor formation by Bcr-Abl-expressing cells were specifically inhibited by this compound [7].
  • Association of the protein kinases c-Bcr and Bcr-Abl with proteins of the 14-3-3 family [5].
  • The sequence of the 3BP-1 protein is similar to that of a COOH-terminal segment of Bcr and to guanosine triphosphatase-activating protein (GAP)-rho, which suggests that it might have GAP activity for Ras-related proteins [8].

Chemical compound and disease context of Bcr


Biological context of Bcr

  • The ability of Bcr-Abl to protect cytokine-dependent 32D myeloid cells from death induced by cytokine deprivation or DNA damage does not, however, require functional NF-kappaB [14].
  • Treatment with LBH589 also depleted Bcr-Abl levels and induced apoptosis of IM-resistant primary human CML cells, including those with expression of Bcr-AblT315I [9].
  • We investigated the role of poly(ADP-ribose) polymerase (PARP) activity in imatinib-induced cell death in Bcr-Abl-positive cells [15].
  • These combined data demonstrate a prominent role for Abr and Bcr in the regulation of glial cell morphology and reactivity, and consequently in granule cell migration during postnatal cerebellar development in mammals [16].
  • In the current study this hypothesis was tested in vivo by introducing a Bcr/Abl P190 transgene into mice lacking endogenous bcr protein [17].

Anatomical context of Bcr

  • Mouse bone marrow cells transduced with retroviral vectors encoding either of two oncogenic Bcr-Abl isoforms (p210(Bcr-Abl) and p185(Bcr-Abl)) induce B cell lympholeukemias when transplanted into lethally irradiated mice [2].
  • Abnormal function of astroglia lacking Abr and Bcr RacGAPs [16].
  • In addition, the Bcr/1-242-Abl mutant has a reduced capacity to induce focus formation in fibroblasts [18].
  • Neoplastic spleens from these mice usually contained b3a2 Bcr-Abl transcripts [3].
  • NS-187 also inhibited leukemic cells harboring wild-type Bcr-Abl growth in the central nervous system, which sometimes becomes a sanctuary for leukemic cells under imatinib treatment [19].

Associations of Bcr with chemical compounds

  • Importantly, this activation is dependent on the tyrosine kinase activity of Bcr-Abl and partially requires Ras [14].
  • Although cells expressing the Bcr-Abl kinase can proliferate in the absence of IL-7, they remain responsive to this cytokine, which can reduce their sensitivity to imatinib [2].
  • AMN107 (Novartis Pharmaceuticals, Basel, Switzerland) has potent in vitro and in vivo activity against the unmutated and most common mutant forms of Bcr-Abl [9].
  • This binding occurs in a phosphotyrosine-dependent manner at Bcr sites of Bcr-Abl [18].
  • Bcr/Abl expression stimulates integrin function in hematopoietic cell lines [20].

Physical interactions of Bcr


Enzymatic interactions of Bcr


Regulatory relationships of Bcr


Other interactions of Bcr

  • This study implicates NF-kappaB as an important component of Bcr-Abl signaling [14].
  • IKK activity is not deregulated by Bcr-Abl and v-Abl [10].
  • Development of NS-187, a potent and selective dual Bcr-Abl/Lyn tyrosine kinase inhibitor [19].
  • Here we demonstrate that the simultaneous disruption of two negative regulators of Rac, Abr and Bcr, in mice leads to specific abnormalities in postnatal cerebellar development [16].
  • Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and resistance due to their loss is overcome by a BH3 mimetic [24].

Analytical, diagnostic and therapeutic context of Bcr


  1. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Kerkelä, R., Grazette, L., Yacobi, R., Iliescu, C., Patten, R., Beahm, C., Walters, B., Shevtsov, S., Pesant, S., Clubb, F.J., Rosenzweig, A., Salomon, R.N., Van Etten, R.A., Alroy, J., Durand, J.B., Force, T. Nat. Med. (2006) [Pubmed]
  2. Arf gene loss enhances oncogenicity and limits imatinib response in mouse models of Bcr-Abl-induced acute lymphoblastic leukemia. Williams, R.T., Roussel, M.F., Sherr, C.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. BCR gene expression blocks Bcr-Abl induced pathogenicity in a mouse model. Lin, F., Monaco, G., Sun, T., Liu, J., Lin, H., Stephens, C., Belmont, J., Arlinghaus, R.B. Oncogene (2001) [Pubmed]
  4. Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia. Hu, Y., Liu, Y., Pelletier, S., Buchdunger, E., Warmuth, M., Fabbro, D., Hallek, M., Van Etten, R.A., Li, S. Nat. Genet. (2004) [Pubmed]
  5. Association of the protein kinases c-Bcr and Bcr-Abl with proteins of the 14-3-3 family. Reuther, G.W., Fu, H., Cripe, L.D., Collier, R.J., Pendergast, A.M. Science (1994) [Pubmed]
  6. Increased neutrophil respiratory burst in bcr-null mutants. Voncken, J.W., van Schaick, H., Kaartinen, V., Deemer, K., Coates, T., Landing, B., Pattengale, P., Dorseuil, O., Bokoch, G.M., Groffen, J. Cell (1995) [Pubmed]
  7. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Druker, B.J., Tamura, S., Buchdunger, E., Ohno, S., Segal, G.M., Fanning, S., Zimmermann, J., Lydon, N.B. Nat. Med. (1996) [Pubmed]
  8. Identification of a protein that binds to the SH3 region of Abl and is similar to Bcr and GAP-rho. Cicchetti, P., Mayer, B.J., Thiel, G., Baltimore, D. Science (1992) [Pubmed]
  9. Combined effects of novel tyrosine kinase inhibitor AMN107 and histone deacetylase inhibitor LBH589 against Bcr-Abl-expressing human leukemia cells. Fiskus, W., Pranpat, M., Bali, P., Balasis, M., Kumaraswamy, S., Boyapalle, S., Rocha, K., Wu, J., Giles, F., Manley, P.W., Atadja, P., Bhalla, K. Blood (2006) [Pubmed]
  10. Mechanisms of Bcr-Abl-mediated NF-kappaB/Rel activation. Kirchner, D., Duyster, J., Ottmann, O., Schmid, R.M., Bergmann, L., Munzert, G. Exp. Hematol. (2003) [Pubmed]
  11. Activity of the Bcr-Abl kinase inhibitor PD180970 against clinically relevant Bcr-Abl isoforms that cause resistance to imatinib mesylate (Gleevec, STI571). La Rosée, P., Corbin, A.S., Stoffregen, E.P., Deininger, M.W., Druker, B.J. Cancer Res. (2002) [Pubmed]
  12. AMN107, a novel aminopyrimidine inhibitor of Bcr-Abl, has in vitro activity against imatinib-resistant chronic myeloid leukemia. Golemovic, M., Verstovsek, S., Giles, F., Cortes, J., Manshouri, T., Manley, P.W., Mestan, J., Dugan, M., Alland, L., Griffin, J.D., Arlinghaus, R.B., Sun, T., Kantarjian, H., Beran, M. Clin. Cancer Res. (2005) [Pubmed]
  13. Abrogation of the cell death response to oxidative stress by the c-Abl tyrosine kinase inhibitor STI571. Kumar, S., Mishra, N., Raina, D., Saxena, S., Kufe, D. Mol. Pharmacol. (2003) [Pubmed]
  14. A requirement for NF-kappaB activation in Bcr-Abl-mediated transformation. Reuther, J.Y., Reuther, G.W., Cortez, D., Pendergast, A.M., Baldwin, A.S. Genes Dev. (1998) [Pubmed]
  15. Role of poly(ADP-ribose) polymerase activity in imatinib mesylate-induced cell death. Moehring, A., Wohlbold, L., Aulitzky, W.E., van der Kuip, H. Cell Death Differ. (2005) [Pubmed]
  16. Abnormal function of astroglia lacking Abr and Bcr RacGAPs. Kaartinen, V., Gonzalez-Gomez, I., Voncken, J.W., Haataja, L., Faure, E., Nagy, A., Groffen, J., Heisterkamp, N. Development (2001) [Pubmed]
  17. Bcr/Abl associated leukemogenesis in bcr null mutant mice. Voncken, J.W., Kaartinen, V., Groffen, J., Heisterkamp, N. Oncogene (1998) [Pubmed]
  18. The SH2-containing adapter protein GRB10 interacts with BCR-ABL. Bai, R.Y., Jahn, T., Schrem, S., Munzert, G., Weidner, K.M., Wang, J.Y., Duyster, J. Oncogene (1998) [Pubmed]
  19. Development of NS-187, a potent and selective dual Bcr-Abl/Lyn tyrosine kinase inhibitor. Kimura, S., Niwa, T., Hirabayashi, K., Maekawa, T. Cancer Chemother. Pharmacol. (2006) [Pubmed]
  20. Bcr/Abl expression stimulates integrin function in hematopoietic cell lines. Bazzoni, G., Carlesso, N., Griffin, J.D., Hemler, M.E. J. Clin. Invest. (1996) [Pubmed]
  21. Resistance to imatinib of bcr/abl p190 lymphoblastic leukemia cells. Mishra, S., Zhang, B., Cunnick, J.M., Heisterkamp, N., Groffen, J. Cancer Res. (2006) [Pubmed]
  22. BCR/ABL P190 transgenic mice develop leukemia in the absence of Crkl. Hemmeryckx, B., Reichert, A., Watanabe, M., Kaartinen, V., de Jong, R., Pattengale, P.K., Groffen, J., Heisterkamp, N. Oncogene (2002) [Pubmed]
  23. Coexistence of phosphotyrosine-dependent and -independent interactions between Cbl and Bcr-Abl. Gaston, I., Johnson, K.J., Oda, T., Bhat, A., Reis, M., Langdon, W., Shen, L., Deininger, M.W., Druker, B.J. Exp. Hematol. (2004) [Pubmed]
  24. Bim and Bad mediate imatinib-induced killing of Bcr/Abl+ leukemic cells, and resistance due to their loss is overcome by a BH3 mimetic. Kuroda, J., Puthalakath, H., Cragg, M.S., Kelly, P.N., Bouillet, P., Huang, D.C., Kimura, S., Ottmann, O.G., Druker, B.J., Villunger, A., Roberts, A.W., Strasser, A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  25. Autocrine secretion of osteopontin results in degradation of I kappa B in Bcr-Abl-expressing cells. Vejda, S., Piwocka, K., McKenna, S.L., Cotter, T.G. Br. J. Haematol. (2005) [Pubmed]
  26. Regional localization and developmental expression of the BCR gene in rodent brain. Fioretos, T., Voncken, J.W., Baram, T.Z., Kamme, F., Groffen, J., Heisterkamp, N. Cell. Mol. Biol. Res. (1995) [Pubmed]
  27. Action of the Src family kinase inhibitor, dasatinib (BMS-354825), on human prostate cancer cells. Nam, S., Kim, D., Cheng, J.Q., Zhang, S., Lee, J.H., Buettner, R., Mirosevich, J., Lee, F.Y., Jove, R. Cancer Res. (2005) [Pubmed]
  28. BCR/ABL-induced leukemogenesis causes phosphorylation of Hef1 and its association with Crkl. de Jong, R., van Wijk, A., Haataja, L., Heisterkamp, N., Groffen, J. J. Biol. Chem. (1997) [Pubmed]
  29. c-CBL is not required for leukemia induction by Bcr-Abl in mice. Dinulescu, D.M., Wood, L.J., Shen, L., Loriaux, M., Corless, C.L., Gross, A.W., Ren, R., Deininger, M.W., Druker, B.J. Oncogene (2003) [Pubmed]
  30. Protein kinase CK2alpha is a target for the Abl and Bcr-Abl tyrosine kinases. Hériché, J.K., Chambaz, E.M. Oncogene (1998) [Pubmed]
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