core binding factor alpha 3 subunit

Summary

Summary: A transcription factor that dimerizes with the cofactor CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain.

Top Publications

  1. Yang N, Zhang L, Zhang Y, Kazazian H. An important role for RUNX3 in human L1 transcription and retrotransposition. Nucleic Acids Res. 2003;31:4929-40 pubmed
  2. Giambra V, Jenkins C, Wang H, Lam S, Shevchuk O, Nemirovsky O, et al. NOTCH1 promotes T cell leukemia-initiating activity by RUNX-mediated regulation of PKC-? and reactive oxygen species. Nat Med. 2012;18:1693-8 pubmed publisher
  3. Lau Q, Raja E, Salto Tellez M, Liu Q, Ito K, Inoue M, et al. RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer. Cancer Res. 2006;66:6512-20 pubmed
    ..Frequent protein mislocalization and methylation could render RUNX3 a valuable marker for early detection and risk assessment. ..
  4. Brenner O, Levanon D, Negreanu V, Golubkov O, Fainaru O, Woolf E, et al. Loss of Runx3 function in leukocytes is associated with spontaneously developed colitis and gastric mucosal hyperplasia. Proc Natl Acad Sci U S A. 2004;101:16016-21 pubmed
    ..Several susceptibility loci were identified on different human chromosomes including the chromosomal region 1p36 where RUNX3 resides. It is thus tempting to speculate that mutations in RUNX3 may constitute an IBD risk factor in humans. ..
  5. Grueter B, Petter M, Egawa T, Laule Kilian K, Aldrian C, Wuerch A, et al. Runx3 regulates integrin alpha E/CD103 and CD4 expression during development of CD4-/CD8+ T cells. J Immunol. 2005;175:1694-705 pubmed
    ..Thus, Runx3 is a main regulator of CD4 silencing and CD103 induction and thus contributes to the phenotype of CD8 SP T cells during thymocyte development. ..
  6. Ito Y. Oncogenic potential of the RUNX gene family: 'overview'. Oncogene. 2004;23:4198-208 pubmed
    ..In this Overview, I will summarize how this growing field has been formed and what are the challenging new frontiers for better understanding of the oncogenic potential of this gene family. ..
  7. Salto Tellez M, Peh B, Ito K, Tan S, Chong P, Han H, et al. RUNX3 protein is overexpressed in human basal cell carcinomas. Oncogene. 2006;25:7646-9 pubmed
    ..Our results indicate that although the deregulation of Wnt signalling could contribute to the pathogenesis of a subset of BCC, RUNX3 appears to be a universal downstream mediator of a constitutively active Shh pathway in BCC. ..
  8. Lu X, Yu J, Ying L, Han J, Wang S, Yu Q, et al. Stepwise cumulation of RUNX3 methylation mediated by Helicobacter pylori infection contributes to gastric carcinoma progression. Cancer. 2012;118:5507-17 pubmed publisher
    ..Runt-related transcription factor 3 (RUNX3) is a candidate tumor suppressor gene whose deficiency is causally related to GC. However, in H. pylori infection-associated GC, the role of RUNX3 has not been studied...
  9. Rennert J, Coffman J, Mushegian A, Robertson A. The evolution of Runx genes I. A comparative study of sequences from phylogenetically diverse model organisms. BMC Evol Biol. 2003;3:4 pubmed
    ..At least two introns were present in the primordial bilaterian Runx gene. Alternative promoter usage arose prior to the duplication events that gave rise to three Runx genes in vertebrates. ..

More Information

Publications62

  1. Wildt K, Sun G, Grueter B, Fischer M, Zamisch M, Ehlers M, et al. The transcription factor Zbtb7b promotes CD4 expression by antagonizing Runx-mediated activation of the CD4 silencer. J Immunol. 2007;179:4405-14 pubmed
    ..These findings demonstrate that the transcription factor Zbtb7b promotes CD4 expression by antagonizing Runx-mediated CD4 repression. ..
  2. Wang L, Wildt K, Castro E, Xiong Y, Feigenbaum L, Tessarollo L, et al. The zinc finger transcription factor Zbtb7b represses CD8-lineage gene expression in peripheral CD4+ T cells. Immunity. 2008;29:876-87 pubmed publisher
    ..We conclude that a key function of Zbtb7b in the mature CD4+ T cell compartment is to repress CD8-lineage gene expression. ..
  3. Kohu K, Ohmori H, Wong W, Onda D, Wakoh T, Kon S, et al. The Runx3 transcription factor augments Th1 and down-modulates Th2 phenotypes by interacting with and attenuating GATA3. J Immunol. 2009;183:7817-24 pubmed publisher
    ..Our results suggest that the balance of Runx3 and GATA3 is one factor that influences the manifestation of CD4(+) cells as the Th1 or Th2 phenotypes. ..
  4. Sakakura C, Miyagawa K, Fukuda K, Nakashima S, Yoshikawa T, Kin S, et al. Frequent silencing of RUNX3 in esophageal squamous cell carcinomas is associated with radioresistance and poor prognosis. Oncogene. 2007;26:5927-38 pubmed
    ..Examination of RUNX3 expression in pretreatment specimens may predict radiosensitivity, and induction of RUNX3 expression may increase tumor radiosensitivity. ..
  5. de Bruijn M, Speck N. Core-binding factors in hematopoiesis and immune function. Oncogene. 2004;23:4238-48 pubmed
    ..We also discuss the later stages of hematopoiesis for which members of the core binding factor family are required, as well as the recently described roles for these proteins in autoimmunity. ..
  6. Huang B, Qu Z, Ong C, Tsang Y, Xiao G, Shapiro D, et al. RUNX3 acts as a tumor suppressor in breast cancer by targeting estrogen receptor ?. Oncogene. 2012;31:527-34 pubmed publisher
    ..By destabilizing ER?, RUNX3 acts as a novel tumor suppressor in breast cancer. ..
  7. Wei D, Gong W, Oh S, Li Q, Kim W, Wang L, et al. Loss of RUNX3 expression significantly affects the clinical outcome of gastric cancer patients and its restoration causes drastic suppression of tumor growth and metastasis. Cancer Res. 2005;65:4809-16 pubmed
    ..Therefore, we offered both clinical and mechanistic evidence that RUNX3 was an independent prognostic factor and a potential therapeutic target for gastric cancer. ..
  8. Arman M, Aguilera Montilla N, Mas V, Puig Kröger A, Pignatelli M, Guigo R, et al. The human CD6 gene is transcriptionally regulated by RUNX and Ets transcription factors in T cells. Mol Immunol. 2009;46:2226-35 pubmed publisher
    ..Therefore, RUNX1/3 and Ets1 control the expression of CD6 in human T lymphocytes, thus expanding the range of T-cell specific and developmentally regulated lymphocyte gene targets involved in T-cell activation and differentiation. ..
  9. Inoue K, Ito K, Osato M, Lee B, Bae S, Ito Y. The transcription factor Runx3 represses the neurotrophin receptor TrkB during lineage commitment of dorsal root ganglion neurons. J Biol Chem. 2007;282:24175-84 pubmed
    ..Taken together, Runx3 determines TrkC positive sensory neuron identities through the transcriptional repression of TrkB when Trk-BTrkC double positive neurons differentiate into TrkC single positive neurons. ..
  10. Balmain A. Cancer: new-age tumour suppressors. Nature. 2002;417:235-7 pubmed
  11. Zhang M, Xie R, Hou W, Wang B, Shen R, Wang X, et al. PTHrP prevents chondrocyte premature hypertrophy by inducing cyclin-D1-dependent Runx2 and Runx3 phosphorylation, ubiquitylation and proteasomal degradation. J Cell Sci. 2009;122:1382-9 pubmed publisher
    ..These results suggest that PTHrP might prevent premature hypertrophy in chondrocytes, at least in part by inducing degradation of Runx2 and Runx3 in a cyclin-D1-dependent manner. ..
  12. Presnell S, Zhang L, Chlebowy C, Al Attar A, Lutz C. Differential transcription factor use by the KIR2DL4 promoter under constitutive and IL-2/15-treated conditions. J Immunol. 2012;188:4394-404 pubmed publisher
    ..Differences between 2DL4 and clonally restricted KIR promoters suggest a model that explains the unique 2DL4 expression pattern in human NK cells. ..
  13. Durst K, Hiebert S. Role of RUNX family members in transcriptional repression and gene silencing. Oncogene. 2004;23:4220-4 pubmed
    ..Thus, transcriptional repression and gene silencing through RUNX1 contribute to the mechanisms of leukemogenesis of the fusion proteins. Therapies directed at the associated cofactors may be beneficial for treatment of these leukemias. ..
  14. 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. ..
  15. Kim E, Kim Y, Jeong P, Ha Y, Bae S, Kim W. Methylation of the RUNX3 promoter as a potential prognostic marker for bladder tumor. J Urol. 2008;180:1141-5 pubmed publisher
    ..RUNX3 promoter methylation status could be a promising marker for assessing the prognosis of human bladder tumors. ..
  16. Ito K, Inoue K, Bae S, Ito Y. Runx3 expression in gastrointestinal tract epithelium: resolving the controversy. Oncogene. 2009;28:1379-84 pubmed publisher
    ..G-poly primarily recognizes the region beyond 234 and hence, is unable to detect Runx3 in this tissue. ..
  17. Peng Z, Tang H, Wang X, Zhou C, Fan J, Wang L, et al. Inhibition of the growth and metastasis of human colon cancer by restoration of RUNX3 expression in cancer cells. Int J Oncol. 2008;33:979-84 pubmed
    ..Collectively, our clinical and experimental data support the notion that RUNX3 is a tumor suppressor in human colon cancer. ..
  18. Lai C, Mager D. Role of runt-related transcription factor 3 (RUNX3) in transcription regulation of natural cytotoxicity receptor 1 (NCR1/NKp46), an activating natural killer (NK) cell receptor. J Biol Chem. 2012;287:7324-34 pubmed publisher
    ..RUNX3 overexpression had the opposite effect. These findings shed light on the role of RUNX3 in the control of an important NK-activating receptor. ..
  19. Kim W, Kim E, Jeong P, Quan C, Kim J, Li Q, et al. RUNX3 inactivation by point mutations and aberrant DNA methylation in bladder tumors. Cancer Res. 2005;65:9347-54 pubmed
  20. Chi X, Yang J, Lee K, Ito K, Sakakura C, Li Q, et al. RUNX3 suppresses gastric epithelial cell growth by inducing p21(WAF1/Cip1) expression in cooperation with transforming growth factor {beta}-activated SMAD. Mol Cell Biol. 2005;25:8097-107 pubmed
    ..Our results suggest that at least part of the tumor suppressor activity of RUNX3 is associated with its ability to induce p21 expression. ..
  21. Bae S, Choi J. Tumor suppressor activity of RUNX3. Oncogene. 2004;23:4336-40 pubmed
    ..The tumorigenicity of human gastric cancer cell lines in nude mice decreased as the level of RUNX3 expression increased, which indicates that RUNX3 is a bona fide tumor suppressor of gastric cancers. ..
  22. Wolff E, Liang G, Cortez C, Tsai Y, Castelao J, Cortessis V, et al. RUNX3 methylation reveals that bladder tumors are older in patients with a history of smoking. Cancer Res. 2008;68:6208-14 pubmed publisher
    ..Because RUNX3 methylation is acquired early on in tumorigenesis, then its detection in biopsy or urine specimens could provide a marker to screen cigarette smokers long before any symptoms of bladder cancer are present. ..
  23. Mikata R, Fukai K, Imazeki F, Arai M, Fujiwara K, Yonemitsu Y, et al. BCL2L10 is frequently silenced by promoter hypermethylation in gastric cancer. Oncol Rep. 2010;23:1701-8 pubmed
    ..In conclusion, our data suggest that silencing of BCL2L10 by aberrant methylation is a common feature in gastric cancer and its inactivation may be involved in the early steps of gastric carcinogenesis. ..
  24. Tsang Y, Lamb A, Romero Gallo J, Huang B, Ito K, Peek R, et al. Helicobacter pylori CagA targets gastric tumor suppressor RUNX3 for proteasome-mediated degradation. Oncogene. 2010;29:5643-50 pubmed publisher
    ..Our studies identify RUNX3 as a novel cellular target of H. pylori CagA and also reveal a mechanism by which CagA functions as an oncoprotein by blocking the activity of gastric tumor suppressor RUNX3. ..
  25. Li L, Li J, Shen Y, Yu L, Zhang J. [Promoter methylation and expression of Runx3 gene in gastric cancer]. Zhonghua Wei Chang Wai Ke Za Zhi. 2008;11:379-82 pubmed
    ..The promoter hypermethylation is a main mechanism of reduced or loss expression of Runx3 gene, which may provide molecular diagnosis and stage evaluation of gastric cancer. ..
  26. Araki K, Osaki M, Nagahama Y, Hiramatsu T, Nakamura H, Ohgi S, et al. Expression of RUNX3 protein in human lung adenocarcinoma: implications for tumor progression and prognosis. Cancer Sci. 2005;96:227-31 pubmed
    ..027). The expression of RUNX3 protein in lung AC might play a pivotal role in tumor progression and patients' survival. ..
  27. Woolf E, Brenner O, Goldenberg D, Levanon D, Groner Y. Runx3 regulates dendritic epidermal T cell development. Dev Biol. 2007;303:703-14 pubmed
    ..Of note, while Runx3(-/-) mice lack both DETCs and Langerhans cells, the two most important components of skin immune surveillance, the mice did not develop skin lesions under pathogen-free (SPF) conditions. ..
  28. 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. ..
  29. Yoshida C, Yamamoto H, Fujita T, Furuichi T, Ito K, Inoue K, et al. Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog. Genes Dev. 2004;18:952-63 pubmed
    ..These findings demonstrate that Runx2 and Runx3 are essential for chondrocyte maturation and that Runx2 regulates limb growth by organizing chondrocyte maturation and proliferation through the induction of Ihh expression. ..
  30. Lee J, Lee D, Bae S, Jung H. Abnormal liver differentiation and excessive angiogenesis in mice lacking Runx3. Histochem Cell Biol. 2013;139:751-8 pubmed publisher
    ..Clarifying the mechanisms of angiogenesis and liver differentiation might aid in the design of efficient and safe antiangiogenic therapy and gene therapy for liver disorders. ..
  31. Lund A, Van Lohuizen M. RUNX: a trilogy of cancer genes. Cancer Cell. 2002;1:213-5 pubmed
    ..Recent data involve RUNX3 as an important tumor suppressor in gastric cancers and pose interesting questions about how perturbed levels and interspecific competition among RUNX family members may contribute to tumorigenesis. ..
  32. Bangsow C, Rubins N, Glusman G, Bernstein Y, Negreanu V, Goldenberg D, et al. The RUNX3 gene--sequence, structure and regulated expression. Gene. 2001;279:221-32 pubmed
    ..Transfection experiments demonstrated that both promoters were highly active in the GM1500 B-cell line, which endogenously expresses RUNX3, but were inactive in the K562 myeloid cell line, which does not express RUNX3. ..
  33. Chuang L, Ito Y. RUNX3 is multifunctional in carcinogenesis of multiple solid tumors. Oncogene. 2010;29:2605-15 pubmed publisher
    ..This review summarizes the important findings that link RUNX3 to tumor suppression. ..
  34. Li Q, Ito K, Sakakura C, Fukamachi H, Inoue K, Chi X, et al. Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell. 2002;109:113-24 pubmed
  35. Shiraha H, Nishina S, Yamamoto K. Loss of runt-related transcription factor 3 causes development and progression of hepatocellular carcinoma. J Cell Biochem. 2011;112:745-9 pubmed publisher
    ..RUNX3 is a promising candidate as a tumor suppressor gene for HCC. ..
  36. Pande S, Ali S, Dowdy C, Zaidi S, Ito K, Ito Y, et al. Subnuclear targeting of the Runx3 tumor suppressor and its epigenetic association with mitotic chromosomes. J Cell Physiol. 2009;218:473-9 pubmed publisher
  37. Stein G, Lian J, Van Wijnen A, Stein J, Montecino M, Javed A, et al. Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression. Oncogene. 2004;23:4315-29 pubmed
  38. Osaki M, Moriyama M, Adachi K, Nakada C, Takeda A, Inoue Y, et al. Expression of RUNX3 protein in human gastric mucosa, intestinal metaplasia and carcinoma. Eur J Clin Invest. 2004;34:605-12 pubmed
  39. Guo C, Ding J, Yao L, Sun L, Lin T, Song Y, et al. Tumor suppressor gene Runx3 sensitizes gastric cancer cells to chemotherapeutic drugs by downregulating Bcl-2, MDR-1 and MRP-1. Int J Cancer. 2005;116:155-60 pubmed
    ..Taken together, our findings suggested that overexpression of Runx3 could sensitize gastric cancer cells to chemotherapeutic drugs by downregulating the Bcl-2, MDR-1 and MRP-1. ..
  40. Ito K, Liu Q, Salto Tellez M, Yano T, Tada K, Ida H, et al. RUNX3, a novel tumor suppressor, is frequently inactivated in gastric cancer by protein mislocalization. Cancer Res. 2005;65:7743-50 pubmed
    ..In addition to the deregulation of mechanisms controlling gene expression, there would also seem to be at least one other mechanism controlling nuclear translocation of RUNX3 that is impaired frequently in gastric cancer. ..
  41. Kim H, Oh B, Choi J, Bae S. Pim-1 kinase phosphorylates and stabilizes RUNX3 and alters its subcellular localization. J Cell Biochem. 2008;105:1048-58 pubmed publisher
    ..Our results demonstrate that the subcellular localization of RUNX3 is altered by phosphorylation. We propose that RUNX family members may behave as oncogenes if mislocalized to a cellular micro-compartment. ..
  42. Subramaniam M, Chan J, Soong R, Ito K, Yeoh K, Wong R, et al. RUNX3 inactivation in colorectal polyps arising through different pathways of colonic carcinogenesis. Am J Gastroenterol. 2009;104:426-36 pubmed publisher
    ..In addition, epigenetic RUNX3 inactivation is a frequent event in the serrated colonic polyps as well as in the ACF of FAP polyps. ..
  43. Kohu K, Sato T, Ohno S, Hayashi K, Uchino R, Abe N, et al. Overexpression of the Runx3 transcription factor increases the proportion of mature thymocytes of the CD8 single-positive lineage. J Immunol. 2005;174:2627-36 pubmed
    ..Thus, Runx3 can drive thymocytes to select the CD4(-)8(+) lineage. This activity is likely to be due to more than a simple silencing of CD4 gene expression. ..
  44. Van Wijnen A, Stein G, Gergen J, Groner Y, Hiebert S, Ito Y, et al. Nomenclature for Runt-related (RUNX) proteins. Oncogene. 2004;23:4209-10 pubmed
  45. Otto F, Lubbert M, Stock M. Upstream and downstream targets of RUNX proteins. J Cell Biochem. 2003;89:9-18 pubmed
    ..Whether a particular RUNX protein specifically targets a defined subset of downstream genes or whether there is some redundancy as to which RUNX protein activates which target promoter remains to be elucidated. ..
  46. Levanon D, Bettoun D, Harris Cerruti C, Woolf E, Negreanu V, Eilam R, et al. The Runx3 transcription factor regulates development and survival of TrkC dorsal root ganglia neurons. EMBO J. 2002;21:3454-63 pubmed
    ..The data provide new genetic insights into the neurogenesis of DRGs and may help elucidate the molecular mechanisms underlying somatosensory-related ataxia in humans. ..
  47. Yamamura Y, Lee W, Inoue K, Ida H, Ito Y. RUNX3 cooperates with FoxO3a to induce apoptosis in gastric cancer cells. J Biol Chem. 2006;281:5267-76 pubmed
    ..These findings show that RUNX3 cooperates with FoxO3a/FKHRL1 to participate in the induction of apoptosis by activating Bim and may play an important role in tumor suppression in gastric cancer. ..
  48. Schulz E, Mariani L, Radbruch A, Hofer T. Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12. Immunity. 2009;30:673-83 pubmed publisher
    ..Thus initial polarization and subsequent imprinting of Th1 cells are mediated by interlinked, sequentially acting positive feedback loops of TCR-interferon-gamma-Stat1-T-bet and interleukin-12-Stat4-T-bet signaling. ..
  49. Hassan H, Sakaguchi S, Tenno M, Kopf A, Boucheron N, Carpenter A, et al. Cd8 enhancer E8I and Runx factors regulate CD8? expression in activated CD8+ T cells. Proc Natl Acad Sci U S A. 2011;108:18330-5 pubmed publisher
    ..Thus, our data suggest an E8(I)- and Runx3/CBF?-dependent epigenetic programming of the Cd8a locus during T-cell activation, leading to Runx/CBF? complex-independent maintenance of CD8? expression in effector T cells. ..
  50. Kim T, Lee H, Hwang K, Lee M, Kim J, Bang Y, et al. Methylation of RUNX3 in various types of human cancers and premalignant stages of gastric carcinoma. Lab Invest. 2004;84:479-84 pubmed
    ..In conclusion, RUNX3 methylation is frequently found in human cancers, including gastric cancer, and is mostly cancer specific, with the exception of the stomach, and thus, might be useful as a potential diagnostic biomarker of cancer. ..
  51. Homma N, Tamura G, Honda T, Matsumoto Y, Nishizuka S, Kawata S, et al. Spreading of methylation within RUNX3 CpG island in gastric cancer. Cancer Sci. 2006;97:51-6 pubmed
    ..The detection of hypermethylation at multiple regions within the RUNX3 CpG island may be useful in the diagnosis and risk assessment of gastric cancer. ..
  52. Levanon D, Brenner O, Otto F, Groner Y. Runx3 knockouts and stomach cancer. EMBO Rep. 2003;4:560-4 pubmed
    ..This article highlights the difficulties of inferring gene function through the interpretation of knockout phenotypes. ..
  53. Chen F, Bai J, Li W, Mei P, Liu H, Li L, et al. RUNX3 suppresses migration, invasion and angiogenesis of human renal cell carcinoma. PLoS ONE. 2013;8:e56241 pubmed publisher
    ..Restoration of RUNX3 expression significantly inhibits RCC cells migration, invasion and angiogenesis. These findings provide new insights into the significance of RUNX3 in migration, invasion and angiogenesis of RCC. ..