core binding factor beta subunit

Summary

Summary: A non-DNA binding transcription factor that is a subunit of core binding factor. It forms heterodimeric complexes with CORE BINDING FACTOR ALPHA SUBUNITS, and regulates GENETIC TRANSCRIPTION of a variety of GENES involved primarily in CELL DIFFERENTIATION and CELL CYCLE progression.

Top Publications

  1. Du J, Zhao K, Rui Y, Li P, Zhou X, Zhang W, et al. Differential requirements for HIV-1 Vif-mediated APOBEC3G degradation and RUNX1-mediated transcription by core binding factor beta. J Virol. 2013;87:1906-11 pubmed publisher
    ..The important interaction domains that are uniquely required for Vif but not RUNX function represent novel targets for the development of HIV inhibitors. ..
  2. Hultquist J, McDougle R, Anderson B, Harris R. HIV type 1 viral infectivity factor and the RUNX transcription factors interact with core binding factor ? on genetically distinct surfaces. AIDS Res Hum Retroviruses. 2012;28:1543-51 pubmed publisher
    ..This mutant still bound RUNX and stimulated RUNX-dependent transcription. These separation-of-function mutants demonstrate that HIV-1 Vif and the RUNX transcription factors interact with cellular CBF? on genetically distinct surfaces. ..
  3. Jäger S, Kim D, Hultquist J, Shindo K, LaRue R, Kwon E, et al. Vif hijacks CBF-β to degrade APOBEC3G and promote HIV-1 infection. Nature. 2011;481:371-5 pubmed publisher
    ..Methods of disrupting the CBF-β-Vif interaction might enable HIV-1 restriction and provide a supplement to current antiviral therapies that primarily target viral proteins. ..
  4. Rudra D, Egawa T, Chong M, Treuting P, Littman D, Rudensky A. Runx-CBFbeta complexes control expression of the transcription factor Foxp3 in regulatory T cells. Nat Immunol. 2009;10:1170-7 pubmed publisher
    ..Thus, Runx-CBFbeta complexes maintain stable high expression of Foxp3 and serve as an essential determinant of T(reg) cell lineage stability. ..
  5. Yoshida C, Furuichi T, Fujita T, Fukuyama R, Kanatani N, Kobayashi S, et al. Core-binding factor beta interacts with Runx2 and is required for skeletal development. Nat Genet. 2002;32:633-8 pubmed
    ..These findings indicate that Cbfbeta is required for the function of Runx2 in skeletal development. ..
  6. Sakakura C, Hagiwara A, Miyagawa K, Nakashima S, Yoshikawa T, Kin S, et al. Frequent downregulation of the runt domain transcription factors RUNX1, RUNX3 and their cofactor CBFB in gastric cancer. Int J Cancer. 2005;113:221-8 pubmed
    ..These findings suggest that RUNX1 and CBFBeta in addition to RUNX3 play some roles in gastric cancers and that roles of RUNX gene family in gastric cancer are more widespread and complex than previously realized. ..
  7. Yokomizo T, Yanagida M, Huang G, Osato M, Honda C, Ema M, et al. Genetic evidence of PEBP2beta-independent activation of Runx1 in the murine embryo. Int J Hematol. 2008;88:134-138 pubmed publisher
    ..5-12.5, although definitive hematopoiesis was not restored. Thus, PEBP2beta-independent Runx1 activation can occur in vivo. This observation sheds new light on the mechanism(s) that regulate the activity of Runx transcription factors. ..
  8. Zhou X, Evans S, Han X, Liu Y, Yu X. Characterization of the interaction of full-length HIV-1 Vif protein with its key regulator CBF? and CRL5 E3 ubiquitin ligase components. PLoS ONE. 2012;7:e33495 pubmed publisher
  9. Hultquist J, Binka M, LaRue R, Simon V, Harris R. Vif proteins of human and simian immunodeficiency viruses require cellular CBF? to degrade APOBEC3 restriction factors. J Virol. 2012;86:2874-7 pubmed publisher

More Information

Publications62

  1. Zhang W, Du J, Evans S, Yu Y, Yu X. T-cell differentiation factor CBF-? regulates HIV-1 Vif-mediated evasion of host restriction. Nature. 2011;481:376-9 pubmed publisher
    ..Considering the importance of the interaction between Vif and CBF-?, disrupting this interaction represents an attractive pharmacological intervention against HIV-1. ..
  2. Roudaia L, Cheney M, Manuylova E, Chen W, Morrow M, Park S, et al. CBFbeta is critical for AML1-ETO and TEL-AML1 activity. Blood. 2009;113:3070-9 pubmed publisher
    ..Similarly, CBFbeta is essential for TEL-AML1's ability to promote self-renewal of B cell precursors in vitro. These studies validate the Runt domain/CBFbeta interaction as a therapeutic target in core binding factor leukemias. ..
  3. Li Z, Lukasik S, Liu Y, Grembecka J, Bielnicka I, Bushweller J, et al. A mutation in the S-switch region of the Runt domain alters the dynamics of an allosteric network responsible for CBFbeta regulation. J Mol Biol. 2006;364:1073-83 pubmed
    ..This study provides an important functional link between dynamic behavior and protein allosteric function, consistent with results on other allosterically regulated proteins. ..
  4. Kanatani N, Fujita T, Fukuyama R, Liu W, Yoshida C, Moriishi T, et al. Cbf beta regulates Runx2 function isoform-dependently in postnatal bone development. Dev Biol. 2006;296:48-61 pubmed
    ..These findings demonstrate that Runx2 isoforms exert their functions through at least partly different mechanisms and Cbfbeta regulates bone development by regulating Runx2 function isoform-dependently. ..
  5. Robertson A, Dickey Sims C, Ransick A, Rupp D, McCarthy J, Coffman J. CBFbeta is a facultative Runx partner in the sea urchin embryo. BMC Biol. 2006;4:4 pubmed publisher
    ..SpCBFbeta is a facultative Runx partner that appears to be required specifically for cell differentiation...
  6. Bollerot K, Romero S, Dunon D, Jaffredo T. Core binding factor in the early avian embryo: cloning of Cbfbeta and combinatorial expression patterns with Runx1. Gene Expr Patterns. 2005;6:29-39 pubmed
    ..By revealing multiple combinatorial patterns between Cbfbeta and Runx1, these data provide new insights into the role of CBF during early development. ..
  7. Chiba N, Watanabe T, Nomura S, Tanaka Y, Minowa M, Niki M, et al. Differentiation dependent expression and distinct subcellular localization of the protooncogene product, PEBP2beta/CBFbeta, in muscle development. Oncogene. 1997;14:2543-52 pubmed
    ..Thus, we could show differentiation dependent pattern of PEBP2beta/CBFbeta expression in muscle development and establish PEBP2beta/CBFbeta to be a cytoplasmic as well as nuclear protein in vivo. ..
  8. Speck N. Core binding factor and its role in normal hematopoietic development. Curr Opin Hematol. 2001;8:192-6 pubmed
    ..Expression studies in fish and frogs and functional analyses in flies indicate that a role for these genes in hematopoiesis is evolutionarily conserved. ..
  9. Sakuma T, Li Q, Jin Y, Choi L, Kim E, Ito K, et al. Cloning and expression pattern of a novel PEBP2 beta-binding protein (charged amino acid rich leucine zipper-1[Crl-1]) in the mouse. Mech Dev. 2001;104:151-4 pubmed
    ..These findings show that this novel PEBP2 beta-interacting protein is expressed mainly in subsets of neuronal cells, suggesting that Crl-1 plays some role in the developing mouse brain. ..
  10. Adya N, Castilla L, Liu P. Function of CBFbeta/Bro proteins. Semin Cell Dev Biol. 2000;11:361-8 pubmed
    ..The ubiquitous expression pattern of the CBFB gene suggests that it may play important roles in many other organ systems. ..
  11. Kundu M, Chen A, Anderson S, Kirby M, Xu L, Castilla L, et al. Role of Cbfb in hematopoiesis and perturbations resulting from expression of the leukemogenic fusion gene Cbfb-MYH11. Blood. 2002;100:2449-56 pubmed
    ..Our data indicate that Cbfb is required for myeloid and lymphoid differentiation; but does not play a critical role in erythroid differentiation. ..
  12. Mendoza Villanueva D, Deng W, Lopez Camacho C, Shore P. The Runx transcriptional co-activator, CBFbeta, is essential for invasion of breast cancer cells. Mol Cancer. 2010;9:171 pubmed publisher
    ..These findings suggest that the interaction between Runx2 and CBFbeta might represent a viable target for therapeutic intervention to inhibit bone metastasis. ..
  13. Wang Q, Stacy T, Miller J, Lewis A, Gu T, Huang X, et al. The CBFbeta subunit is essential for CBFalpha2 (AML1) function in vivo. Cell. 1996;87:697-708 pubmed
    ..Here we demonstrate that homozygous mutation of the Cbfb gene results in the same phenotype. Our results demonstrate that the CBFbeta subunit is required for CBFalpha2 function in vivo. ..
  14. Cammenga J, Niebuhr B, Horn S, Bergholz U, Putz G, Buchholz F, et al. RUNX1 DNA-binding mutants, associated with minimally differentiated acute myelogenous leukemia, disrupt myeloid differentiation. Cancer Res. 2007;67:537-45 pubmed
    ..We propose that RDB mutants antagonize Runx1 function in early progenitors by disrupting a critical balance between DNA-binding-independent and DNA-binding-dependent signaling. ..
  15. Setoguchi R, Tachibana M, Naoe Y, Muroi S, Akiyama K, Tezuka C, et al. Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T cell development. Science. 2008;319:822-5 pubmed publisher
    ..Identification of the transcription factors network in CD4 and CD8 lineage choice provides insight into how distinct T cell subsets are developed for regulating the adaptive immune system. ..
  16. Sasaki K, Yagi H, Bronson R, Tominaga K, Matsunashi T, Deguchi K, et al. Absence of fetal liver hematopoiesis in mice deficient in transcriptional coactivator core binding factor beta. Proc Natl Acad Sci U S A. 1996;93:12359-63 pubmed
    ..These data suggest that Cbfb is essential for definitive hematopoiesis in liver, especially for the commitment to early hematopoietic precursor cells. ..
  17. Tanaka Y, Watanabe T, Chiba N, Niki M, Kuroiwa Y, Nishihira T, et al. The protooncogene product, PEBP2beta/CBFbeta, is mainly located in the cytoplasm and has an affinity with cytoskeletal structures. Oncogene. 1997;15:677-83 pubmed
    ..Thus, the present study extends PEBP2beta/CBFbeta to be a cytoskeleton-affinitive as well as nuclear protein. The implications of these results are discussed. ..
  18. Meder B, Just S, Vogel B, Rudloff J, Gärtner L, Dahme T, et al. JunB-CBFbeta signaling is essential to maintain sarcomeric Z-disc structure and when defective leads to heart failure. J Cell Sci. 2010;123:2613-20 pubmed publisher
  19. Zhou X, Han X, Zhao K, Du J, Evans S, Wang H, et al. Dispersed and conserved hydrophobic residues of HIV-1 Vif are essential for CBF? recruitment and A3G suppression. J Virol. 2014;88:2555-63 pubmed publisher
    ..Therefore, information from this study will help people to further understand how Vif acts against host antiviral mechanism, which is important for novel anti-HIV-1 drug development. ..
  20. Romero Prado M, Blazquez C, Rodríguez Navas C, Muñoz J, Guerrero I, Delgado Baeza E, et al. Functional characterization of human mesenchymal stem cells that maintain osteochondral fates. J Cell Biochem. 2006;98:1457-70 pubmed
    ..These specific cellular conditions match those observed during endochondral bone formation. ..
  21. Bruno L, Mazzarella L, Hoogenkamp M, Hertweck A, Cobb B, Sauer S, et al. Runx proteins regulate Foxp3 expression. J Exp Med. 2009;206:2329-37 pubmed publisher
    ..Our data show that Runx and Foxp3 are components of a feed-forward loop in which Runx proteins contribute to the expression of Foxp3 and cooperate with Foxp3 proteins to regulate the expression of downstream target genes. ..
  22. Brady G, Elgueta Karstegl C, Farrell P. Novel function of the unique N-terminal region of RUNX1c in B cell growth regulation. Nucleic Acids Res. 2013;41:1555-68 pubmed publisher
    ..Remarkably, a cell-penetrating peptide containing the N-terminal sequence of RUNX1c specifically antagonizes the growth inhibitory effect in B lymphoblastoid cells and might be used to modulate the function of human RUNX1c. ..
  23. Johnson K, Zhu S, Tremblay M, Payette J, Wang J, Bouchez L, et al. A stem cell-based approach to cartilage repair. Science. 2012;336:717-21 pubmed publisher
    ..This work provides new insights into the control of chondrogenesis that may ultimately lead to a stem cell-based therapy for osteoarthritis. ..
  24. Matheny C, Speck M, Cushing P, Zhou Y, Corpora T, Regan M, et al. Disease mutations in RUNX1 and RUNX2 create nonfunctional, dominant-negative, or hypomorphic alleles. EMBO J. 2007;26:1163-75 pubmed
    ..We conclude that hypomorphic RUNX2 alleles can cause CCD, whereas hematopoietic disease requires more severely inactivating RUNX1 mutations. ..
  25. Chen C, Li Z, Lu Q, Liu Z. [Establishment of a new method for screening of CBFB-MYH11 fusion gene in acute myeloid leukemia and its value in clinical use]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2012;20:1077-81 pubmed
    ..This method is fast, comprehensive, sensitive, specific, reliable, and should consider to be a robust tool for identification and management of AML patients with CBFB-MYH11 fusion gene. ..
  26. Aventin A, Espadaler M, Casas S, Duarte J, Nomdedeu J, Sierra J. Chromosome 16 inversion-associated translocations in acute myeloid leukemia elucidated using a dual-color CBFB DNA probe. Cancer Genet Cytogenet. 2002;134:142-4 pubmed
    ..We suggest that all cases with inv(16)(p13q22) should be investigated by FISH with appropriate probes for a possible translocation of 16q22-->qter to another chromosome. ..
  27. Malim M. HIV: Ringside views. Nature. 2014;505:167-8 pubmed publisher
  28. Kundu M, Javed A, Jeon J, Horner A, Shum L, Eckhaus M, et al. Cbfbeta interacts with Runx2 and has a critical role in bone development. Nat Genet. 2002;32:639-44 pubmed
    ..Our findings raise the possibility that mutations in CBFB may be responsible for some cases of cleidocranial dysplasia that are not linked to mutations in RUNX2. ..
  29. Ogawa E, Inuzuka M, Maruyama M, Satake M, Naito Fujimoto M, Ito Y, et al. Molecular cloning and characterization of PEBP2 beta, the heterodimeric partner of a novel Drosophila runt-related DNA binding protein PEBP2 alpha. Virology. 1993;194:314-31 pubmed
    ..Furthermore, this heterodimerization was shown to cause a marked increase in the intrinsic DNA binding affinity of the alpha subunit. ..
  30. Blyth K, Vaillant F, Jenkins A, McDonald L, Pringle M, Huser C, et al. Runx2 in normal tissues and cancer cells: A developing story. Blood Cells Mol Dis. 2010;45:117-23 pubmed publisher
    ..Furthermore, we review the evidence that RUNX2 promotes neoplastic development in haematopoietic lineages and in advanced mammary and prostate cancer. ..
  31. Barton J, Bunka D, Knowling S, Lefevre P, Warren A, Bonifer C, et al. Characterization of RNA aptamers that disrupt the RUNX1-CBFbeta/DNA complex. Nucleic Acids Res. 2009;37:6818-30 pubmed publisher
    ..These aptamers represent new reagents that target a novel surface on the RHD required to stabilize the recombinant RHD-CBFbeta complex and thus will further aid exploring the functions of this key transcription factor. ..
  32. Takarada T, Yoneda Y. Transactivation by Runt related factor-2 of matrix metalloproteinase-13 in astrocytes. Neurosci Lett. 2009;451:99-104 pubmed publisher
    ..These results suggest that Runx2 signal input may lead to transactivation of MMP13 gene without affecting OPN expression in astrocytes. ..
  33. Fribourgh J, Nguyen H, Wolfe L, Dewitt D, Zhang W, Yu X, et al. Core binding factor beta plays a critical role by facilitating the assembly of the Vif-cullin 5 E3 ubiquitin ligase. J Virol. 2014;88:3309-19 pubmed publisher
    ..This study advances our understanding of how CBF? facilitates the Vif-mediated degradation of APOBEC3 proteins. ..
  34. Kurosaka H, Islam M, Kuremoto K, Hayano S, Nakamura M, Kawanabe N, et al. Core binding factor beta functions in the maintenance of stem cells and orchestrates continuous proliferation and differentiation in mouse incisors. Stem Cells. 2011;29:1792-803 pubmed publisher
    ..In addition, Runx genes also orchestrate continuous proliferation and differentiation by maintaining the expression of Fgf9 and Shh mRNA. ..
  35. Goyama S, Schibler J, Cunningham L, Zhang Y, Rao Y, Nishimoto N, et al. Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells. J Clin Invest. 2013;123:3876-88 pubmed publisher
    ..Our study unveiled an unexpected prosurvival role for RUNX1 in myeloid leukemogenesis. Inhibiting RUNX1 activity rather than enhancing it could be a promising therapeutic strategy for AMLs with leukemogenic fusion proteins. ..
  36. Bowers S, Calero Nieto F, Valeaux S, Fernandez Fuentes N, Cockerill P. Runx1 binds as a dimeric complex to overlapping Runx1 sites within a palindromic element in the human GM-CSF enhancer. Nucleic Acids Res. 2010;38:6124-34 pubmed publisher
  37. Han M, Kim H, Wee H, Lim K, Park N, Bae S, et al. The cleidocranial dysplasia-related R131G mutation in the Runt-related transcription factor RUNX2 disrupts binding to DNA but not CBF-beta. J Cell Biochem. 2010;110:97-103 pubmed publisher
    ..Retention of specific functions including nuclear localization and binding to CBF-beta of the RUNX2(R131G) mutation may render the mutant protein an effective competitor that interferes with wild-type function...
  38. Weckerle A, Santra M, Ng M, Koty P, Wang Y. CBFB and MYH11 in inv(16)(p13q22) of acute myeloid leukemia displaying close spatial proximity in interphase nuclei of human hematopoietic stem cells. Genes Chromosomes Cancer. 2011;50:746-55 pubmed publisher
    ..Consistent with previous studies, our results suggest that gene proximity may play a role in the formation of cancer-causing rearrangements, providing insight into the mechanism of chromosomal abnormalities in human tumors. ..
  39. Park S, Lim J, Kang C. Crlz1 activates transcription by mobilizing cytoplasmic CBFbeta into the nucleus. Biochim Biophys Acta. 2009;1789:702-8 pubmed publisher
  40. Cunningham L, Finckbeiner S, Hyde R, Southall N, Marugan J, Yedavalli V, et al. Identification of benzodiazepine Ro5-3335 as an inhibitor of CBF leukemia through quantitative high throughput screen against RUNX1-CBF? interaction. Proc Natl Acad Sci U S A. 2012;109:14592-7 pubmed publisher
    ..Our data thus confirmed that RUNX1-CBF? interaction can be targeted for leukemia treatment and we have identified a promising lead compound for this purpose. ..
  41. Salter J, Lippa G, Belashov I, Wedekind J. Core-binding factor ? increases the affinity between human Cullin 5 and HIV-1 Vif within an E3 ligase complex. Biochemistry. 2012;51:8702-4 pubmed publisher
    ..An additional interface between Cul5 and an N-terminal region of Vif appears to be plausible, which has therapeutic design implications. ..
  42. Hart S, Foroni L. Core binding factor genes and human leukemia. Haematologica. 2002;87:1307-23 pubmed
  43. Bae S, Takahashi E, Zhang Y, Ogawa E, Shigesada K, Namba Y, et al. Cloning, mapping and expression of PEBP2 alpha C, a third gene encoding the mammalian Runt domain. Gene. 1995;159:245-8 pubmed
    ..11-p36.13 in the human chromosome and encodes a 415-aa protein. PEBP2 alpha C forms a heterodimer with PEBP2 beta, binds to the PEBP2 site and transactivates transcription, similar to PEBP2 alpha A and PEBP2 alpha B. ..
  44. Han X, Liang W, Hua D, Zhou X, Du J, Evans S, et al. Evolutionarily conserved requirement for core binding factor beta in the assembly of the human immunodeficiency virus/simian immunodeficiency virus Vif-cullin 5-RING E3 ubiquitin ligase. J Virol. 2014;88:3320-8 pubmed publisher
    ..Considering the importance of the interaction between Vif and CBF-? in viral CRL5 function and HIV-1 replication, disrupting this interaction is an attractive strategy against HIV-1. ..
  45. Chen M, Li Y, De Obaldia M, Yang Q, Yzaguirre A, Yamada Inagawa T, et al. Erythroid/myeloid progenitors and hematopoietic stem cells originate from distinct populations of endothelial cells. Cell Stem Cell. 2011;9:541-52 pubmed publisher
    ..The data indicate that EMPs and HSCs differentiate from distinct populations of hemogenic endothelial cells, with Ly6a expression specifically marking the HSC-generating hemogenic endothelium...
  46. Huang G, Zhao X, Wang L, Elf S, Xu H, Zhao X, et al. The ability of MLL to bind RUNX1 and methylate H3K4 at PU.1 regulatory regions is impaired by MDS/AML-associated RUNX1/AML1 mutations. Blood. 2011;118:6544-52 pubmed publisher
    ..1 regulatory regions, and decreased PU.1 expression. The interaction between MLL and AML1 provides a mechanism for the sequence-specific binding of MLL to DNA, and identifies RUNX1 target genes as potential effectors of MLL function. ..
  47. Kim H, Kojima K, Swindle C, Cotta C, Huo Y, Reddy V, et al. FLT3-ITD cooperates with inv(16) to promote progression to acute myeloid leukemia. Blood. 2008;111:1567-74 pubmed
    ..These results indicate that FLT3-activating mutations can cooperate with CBFbeta-SMMHC in an animal model of inv(16)-associated AML. ..
  48. Tobal K, Johnson P, Saunders M, Harrison C, Liu Yin J. Detection of CBFB/MYH11 transcripts in patients with inversion and other abnormalities of chromosome 16 at presentation and remission. Br J Haematol. 1995;91:104-8 pubmed
    ..Though RT-PCR is highly sensitive in detecting CBFB/MYH11 fusion transcripts during remission, monitoring of minimal residual disease in patients with inv(16) remains to be established. ..
  49. Bernard O. [Mechanisms of leucemogenesis]. Bull Cancer. 2010;97:1381-8 pubmed publisher
    ..From these data, the development of efficient therapeutic approaches will be possible by targeting the early oncogenic events which are at the origin of the malignant transformation. ..
  50. Martensson A, Xie X, Persson C, Holm M, Grundstrom T, Mårtensson I. PEBP2 and c-myb sites crucial for lambda5 core enhancer activity in pre-B cells. Eur J Immunol. 2001;31:3165-74 pubmed
    ..Thus, c-myb may be involved in determining the stage-specific expression of the lambda5 gene. ..
  51. Guo Y, Dong L, Qiu X, Wang Y, Zhang B, Liu H, et al. Structural basis for hijacking CBF-? and CUL5 E3 ligase complex by HIV-1 Vif. Nature. 2014;505:229-33 pubmed publisher
    ..Together, our data reveal the structural basis for Vif hijacking of the CBF-? and CUL5 E3 ligase complex, laying a foundation for rational design of novel anti-HIV drugs. ..
  52. Choi A, Illendula A, Pulikkan J, Roderick J, Tesell J, Yu J, et al. RUNX1 is required for oncogenic Myb and Myc enhancer activity in T-cell acute lymphoblastic leukemia. Blood. 2017;130:1722-1733 pubmed publisher
    ..These studies provide genetic and pharmacologic evidence that RUNX1 has oncogenic roles and reveal RUNX1 as a novel therapeutic target in T-ALL. ..
  53. Tenno M, Shiroguchi K, Muroi S, Kawakami E, Koseki K, Kryukov K, et al. Cbfβ2 deficiency preserves Langerhans cell precursors by lack of selective TGFβ receptor signaling. J Exp Med. 2017;214:2933-2946 pubmed publisher
    ..Collectively, our results reveal an essential requirement for the Cbfβ2 variant in LC differentiation and provide novel insight into how the establishment and homeostasis of the LC network is regulated. ..