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Gene Review

CBFB  -  core-binding factor, beta subunit

Homo sapiens

Synonyms: CBF-beta, Core-binding factor subunit beta, PEA2-beta, PEBP2-beta, PEBP2B, ...
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Disease relevance of CBFB


High impact information on CBFB

  • Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia [5].
  • The repeated coiled coil of SMMHC may result in dimerization of the CBF beta fusion protein, which in turn would lead to alterations in transcriptional regulation and contribute to leukemic transformation [5].
  • Reintroduction of CBFbeta into JunB-deficient ECs rescued the tube formation defect and MMP-13 expression, indicating an important role for CBFbeta in EC morphogenesis [6].
  • The AML1-CBF beta transcription factor complex is the most frequent target of specific chromosome translocations in human leukemia [7].
  • Furthermore, the interaction of AML1 with CBFbeta is essential for haematopoiesis [8].

Chemical compound and disease context of CBFB


Biological context of CBFB


Anatomical context of CBFB

  • This rearrangement fuses the CBFB and MYH11 genes, with the latter encoding the smooth muscle myosin heavy chain (SMMHC) [15].
  • We have previously shown that a CBFB-MYH11 cDNA construct can produce a chimeric protein and transform NIH 3T3 cells [13].
  • This system will be useful in examining the effects of CBFbeta-SMMHC on gene expression in the human preleukemic cell, in characterizing the effect of this oncogene on human stem cell biology, and in defining its contribution to the development of leukemia [16].
  • These observations suggest that CBFbeta-SMMHC plays a dominant negative role by sequestering CBFalpha2 into cytoskeletal filaments and aggregates, thereby disrupting CBFalpha2-mediated regulation of gene expression [17].
  • On the other hand, CBFbeta-SMMHC formed filament-like structures that colocalized with actin filaments [17].

Associations of CBFB with chemical compounds

  • The CBFB promoter region has typical features of a housekeeping gene, including high G+C content, high frequency of CpG dinucleotides, and lack of canonical TATA and CCAAT boxes [14].
  • The closed to open transition can be induced by CBFbeta alone; suggesting that one role of CBFbeta is to trigger the S-switch and to stabilize the Runt domain in a conformation enhanced for DNA binding.A feature of the Runt domain hitherto unobserved in any Ig-like DNA-binding domain is the presence of two specifically bound chloride ions [18].
  • A Mutation in the S-switch Region of the Runt Domain Alters the Dynamics of an Allosteric Network Responsible for CBFbeta Regulation [19].

Physical interactions of CBFB

  • Although CBFB forms a core-binding factor transcriptional complex with RUNX1, previous analyses have excluded the CBFB gene as the leukemia-predisposing gene in these families [20].
  • Core binding factors (CBFs) are heterodimeric transcription factors consisting of a DNA-binding CBF alpha subunit and non-DNA-binding CBF beta subunit [21].
  • CBFalpha and CBFbeta are core-binding proteins which have been identified as transcription regulators of hematopoietic genes and shown to be altered in numerous leukemias [22].

Co-localisations of CBFB


Regulatory relationships of CBFB


Other interactions of CBFB

  • Here, we describe the crystal structure of the uncomplexed RUNX1 Runt domain at 1.25A resolution and compare its conformation to previously published structures in complex with DNA, CBFbeta or both [18].
  • Isothermal titration calorimetry results show that this fusion protein binds the Runt domain from Runx1 (CBF alpha) with higher affinity than the native CBF beta protein [11].
  • This hypothesis was confirmed by the detection of deletions of the 3' regions of the CBFB and the MLL genes in AML M4 patients with inv(16) and in patients with ALL and AML associated with MLL gene translocations, respectively [25].
  • Inversion of chromosome 16 and uncommon rearrangements of the CBFB and MYH11 genes in therapy-related acute myeloid leukemia: rare events related to DNA-topoisomerase II inhibitors [9]?

Analytical, diagnostic and therapeutic context of CBFB

  • A very high molecular weight protein/DNA complex is generated when nuclear extracts from patient cells are used in electrophoretic mobility shift assays, as seen in NIH 3T3 cells transfected with the CBFB-MYH11 cDNA [13].
  • Molecular analysis of BM cells using RT-PCR identified a CBFB-MYH11 fusion transcript type D. After achieving complete remission, the patient relapsed [26].
  • A fluorescence in situ hybridization analysis, using the BAC probe spanning the CBFB locus at 16q22.1, revealed that the CBFB probe hybridized to only one of the two homologous chromosome 16 regions [27].
  • To assess the presence of type A CBFB/MYH11 fusion transcripts in five AML-M4Eo patients in remission, we designed a sensitive assay combining nested PCR and allele-specific amplification (NPASA) [28].
  • Recently, the molecular cloning of teh breakpoints has led to the identification of the two fused genes, CBFB on 16q and MYH11 on 16p [28].


  1. Failure of embryonic hematopoiesis and lethal hemorrhages in mouse embryos heterozygous for a knocked-in leukemia gene CBFB-MYH11. Castilla, L.H., Wijmenga, C., Wang, Q., Stacy, T., Speck, N.A., Eckhaus, M., Marín-Padilla, M., Collins, F.S., Wynshaw-Boris, A., Liu, P.P. Cell (1996) [Pubmed]
  2. Solution structure of core binding factor beta and map of the CBF alpha binding site. Huang, X., Peng, J.W., Speck, N.A., Bushweller, J.H. Nat. Struct. Biol. (1999) [Pubmed]
  3. Identification of genes that synergize with Cbfb-MYH11 in the pathogenesis of acute myeloid leukemia. Castilla, L.H., Perrat, P., Martinez, N.J., Landrette, S.F., Keys, R., Oikemus, S., Flanegan, J., Heilman, S., Garrett, L., Dutra, A., Anderson, S., Pihan, G.A., Wolff, L., Liu, P.P. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Frequent downregulation of the runt domain transcription factors RUNX1, RUNX3 and their cofactor CBFB in gastric cancer. Sakakura, C., Hagiwara, A., Miyagawa, K., Nakashima, S., Yoshikawa, T., Kin, S., Nakase, Y., Ito, K., Yamagishi, H., Yazumi, S., Chiba, T., Ito, Y. Int. J. Cancer (2005) [Pubmed]
  5. Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia. Liu, P., Tarlé, S.A., Hajra, A., Claxton, D.F., Marlton, P., Freedman, M., Siciliano, M.J., Collins, F.S. Science (1993) [Pubmed]
  6. JunB is required for endothelial cell morphogenesis by regulating core-binding factor {beta}. Licht, A.H., Pein, O.T., Florin, L., Hartenstein, B., Reuter, H., Arnold, B., Lichter, P., Angel, P., Schorpp-Kistner, M. J. Cell Biol. (2006) [Pubmed]
  7. Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein. Kitabayashi, I., Aikawa, Y., Nguyen, L.A., Yokoyama, A., Ohki, M. EMBO J. (2001) [Pubmed]
  8. Structural basis for the heterodimeric interaction between the acute leukaemia-associated transcription factors AML1 and CBFbeta. Warren, A.J., Bravo, J., Williams, R.L., Rabbitts, T.H. EMBO J. (2000) [Pubmed]
  9. Inversion of chromosome 16 and uncommon rearrangements of the CBFB and MYH11 genes in therapy-related acute myeloid leukemia: rare events related to DNA-topoisomerase II inhibitors? Dissing, M., Le Beau, M.M., Pedersen-Bjergaard, J. J. Clin. Oncol. (1998) [Pubmed]
  10. Molecular diagnostics in the treatment of leukemia. Rubnitz, J.E., Pui, C.H. Curr. Opin. Hematol. (1999) [Pubmed]
  11. Altered affinity of CBF beta-SMMHC for Runx1 explains its role in leukemogenesis. Lukasik, S.M., Zhang, L., Corpora, T., Tomanicek, S., Li, Y., Kundu, M., Hartman, K., Liu, P.P., Laue, T.M., Biltonen, R.L., Speck, N.A., Bushweller, J.H. Nat. Struct. Biol. (2002) [Pubmed]
  12. Zebrafish homolog of the leukemia gene CBFB: its expression during embryogenesis and its relationship to scl and gata-1 in hematopoiesis. Blake, T., Adya, N., Kim, C.H., Oates, A.C., Zon, L., Chitnis, A., Weinstein, B.M., Liu, P.P. Blood (2000) [Pubmed]
  13. Identification of the chimeric protein product of the CBFB-MYH11 fusion gene in inv(16) leukemia cells. Liu, P.P., Wijmenga, C., Hajra, A., Blake, T.B., Kelley, C.A., Adelstein, R.S., Bagg, A., Rector, J., Cotelingam, J., Willman, C.L., Collins, F.S. Genes Chromosomes Cancer (1996) [Pubmed]
  14. Structure of the leukemia-associated human CBFB gene. Hajra, A., Collins, F.S. Genomics (1995) [Pubmed]
  15. CBFB-SMMHC is correlated with increased calreticulin expression and suppresses the granulocytic differentiation factor CEBPA in AML with inv(16). Helbling, D., Mueller, B.U., Timchenko, N.A., Schardt, J., Eyer, M., Betts, D.R., Jotterand, M., Meyer-Monard, S., Fey, M.F., Pabst, T. Blood (2005) [Pubmed]
  16. Human CD34+ cells expressing the inv(16) fusion protein exhibit a myelomonocytic phenotype with greatly enhanced proliferative ability. Wunderlich, M., Krejci, O., Wei, J., Mulloy, J.C. Blood (2006) [Pubmed]
  17. The leukemic protein core binding factor beta (CBFbeta)-smooth-muscle myosin heavy chain sequesters CBFalpha2 into cytoskeletal filaments and aggregates. Adya, N., Stacy, T., Speck, N.A., Liu, P.P. Mol. Cell. Biol. (1998) [Pubmed]
  18. The RUNX1 Runt domain at 1.25A resolution: a structural switch and specifically bound chloride ions modulate DNA binding. Bäckström, S., Wolf-Watz, M., Grundström, C., Härd, T., Grundström, T., Sauer, U.H. J. Mol. Biol. (2002) [Pubmed]
  19. A Mutation in the S-switch Region of the Runt Domain Alters the Dynamics of an Allosteric Network Responsible for CBFbeta Regulation. Li, Z., Lukasik, S.M., Liu, Y., Grembecka, J., Bielnicka, I., Bushweller, J.H., Speck, N.A. J. Mol. Biol. (2006) [Pubmed]
  20. Chromosome band 16q22-linked familial AML: exclusion of candidate genes, and possible disease risk modification by NQO1 polymorphisms. Escher, R., Jones, A., Hagos, F., Carmichael, C., Horwitz, M., Olopade, O.I., Scott, H.S. Genes Chromosomes Cancer (2004) [Pubmed]
  21. Structural and functional characterization of Runx1, CBF beta, and CBF beta-SMMHC. Zhang, L., Lukasik, S.M., Speck, N.A., Bushweller, J.H. Blood Cells Mol. Dis. (2003) [Pubmed]
  22. Functional G-CSF pathways in t(8;21) leukemic cells allow for differentiation induction and degradation of AML1-ETO. Da Silva, N., Meyer-Monard, S., Menot, M.L., Parrado, A., Lebel, A., Balitrand, N., Fenaux, P., Micléa, J.M., Rousselot, P., Degos, L., Dombret, H., Chomienne, C. Hematol. J. (2000) [Pubmed]
  23. The protooncogene product, PEBP2beta/CBFbeta, is mainly located in the cytoplasm and has an affinity with cytoskeletal structures. Tanaka, Y., Watanabe, T., Chiba, N., Niki, M., Kuroiwa, Y., Nishihira, T., Satomi, S., Ito, Y., Satake, M. Oncogene (1997) [Pubmed]
  24. In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: implications for mechanisms of pathogenesis. Michaud, J., Wu, F., Osato, M., Cottles, G.M., Yanagida, M., Asou, N., Shigesada, K., Ito, Y., Benson, K.F., Raskind, W.H., Rossier, C., Antonarakis, S.E., Israels, S., McNicol, A., Weiss, H., Horwitz, M., Scott, H.S. Blood (2002) [Pubmed]
  25. Primary chromosomal rearrangements of leukemia are frequently accompanied by extensive submicroscopic deletions and may lead to altered prognosis. Kolomietz, E., Al-Maghrabi, J., Brennan, S., Karaskova, J., Minkin, S., Lipton, J., Squire, J.A. Blood (2001) [Pubmed]
  26. Variant three-way translocation of inversion 16 in AML-M4Eo confirmed by fluorescence in situ hybridization analysis. Martinez-Climent, J.A., Comes, A.M., Vizcarra, E., Reshmi, S., Benet, I., Marugan, I., Tormo, M., Terol, M.J., Solano, C., Arbona, C., Prosper, F., Barragan, E., Bolufer, P., Rowley, J.D., García-Conde, J. Cancer Genet. Cytogenet. (1999) [Pubmed]
  27. Large fontanelles are a shared feature of haploinsufficiency of RUNX2 and its co-activator CBFB. Goto, T., Aramaki, M., Yoshihashi, H., Nishimura, G., Hasegawa, Y., Takahashi, T., Ishii, T., Fukushima, Y., Kosaki, K. Congenital anomalies. (2004) [Pubmed]
  28. Detection of minimal residual disease in acute myelomonocytic leukemia with abnormal marrow eosinophils by nested polymerase chain reaction with allele specific amplification. Hébert, J., Cayuela, J.M., Daniel, M.T., Berger, R., Sigaux, F. Blood (1994) [Pubmed]
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