1cmo › Citations

Immunoglobulin motif DNA recognition and heterodimerization of the PEBP2/CBF Runt domain.

Nagata T, Gupta V, Sorce D, Kim WY, Sali A, Chait BT, Shigesada K, Ito Y, Werner MH
Nat Struct Biol 6 615-9 (1999)
Cited: 62 times
EuropePMC logo PMID: 10404214

Abstract

The polyomavirus enhancer binding protein 2 (PEBP2) or core binding factor (CBF) is a heterodimeric enhancer binding protein that is associated with genetic regulation of hematopoiesis and osteogenesis. Aberrant forms of PEBP2/CBF are implicated in the cause of the acute human leukemias and in a disorder of bone development known as cleidocranial dysplasia. The common denominator in the natural and mutant forms of this protein is a highly conserved domain of PEBP2/CBF alpha, termed the Runt domain (RD), which is responsible for both DNA binding and heterodimerization with the beta subunit of PEBP2/CBF. The three-dimensional structure of the RD bound to DNA has been determined to be an S-type immunoglobulin fold, establishing a structural relationship between the RD and the core DNA binding domains of NF-kappaB, NFAT1, p53 and the STAT proteins. NMR spectroscopy of a 43.6 kD RD-beta-DNA ternary complex identified the surface of the RD in contact with the beta subunit, suggesting a mechanism for the enhancement of RD DNA binding by beta. Analysis of leukemogenic mutants within the RD provides molecular insights into the role of this factor in leukemogenesis and cleidocranial dysplasia.

Reviews - 1cmo mentioned but not cited (1)

  1. Overview of protein structural and functional folds. Sun PD, Foster CE, Boyington JC. Curr Protoc Protein Sci Chapter 17 Unit 17.1 (2004)

Articles - 1cmo mentioned but not cited (3)

  1. Structural basis for the heterodimeric interaction between the acute leukaemia-associated transcription factors AML1 and CBFbeta. Warren AJ, Bravo J, Williams RL, Rabbitts TH. EMBO J 19 3004-3015 (2000)
  2. Prediction of the structural motifs of sandwich proteins. Fokas AS, Gelfand IM, Kister AE. Proc Natl Acad Sci U S A 101 16780-16783 (2004)
  3. New insights into transcriptional and leukemogenic mechanisms of AML1-ETO and E2A fusion proteins. Li J, Guo C, Steinauer N, Zhang J. Front Biol (Beijing) 11 285-304 (2016)


Reviews citing this publication (23)

  1. Core-binding factors in haematopoiesis and leukaemia. Speck NA, Gilliland DG. Nat Rev Cancer 2 502-513 (2002)
  2. Oncogenic potential of the RUNX gene family: 'overview'. Ito Y. Oncogene 23 4198-4208 (2004)
  3. Point mutations in the RUNX1/AML1 gene: another actor in RUNX leukemia. Osato M. Oncogene 23 4284-4296 (2004)
  4. Mutations in the RUNX2 gene in patients with cleidocranial dysplasia. Otto F, Kanegane H, Mundlos S. Hum Mutat 19 209-216 (2002)
  5. Role of the transcription factor AML-1 in acute leukemia and hematopoietic differentiation. Lutterbach B, Hiebert SW. Gene 245 223-235 (2000)
  6. Molecular basis of tissue-specific gene expression mediated by the runt domain transcription factor PEBP2/CBF. Ito Y. Genes Cells 4 685-696 (1999)
  7. AML1 and the AML1-ETO fusion protein in the pathogenesis of t(8;21) AML. Licht JD. Oncogene 20 5660-5679 (2001)
  8. RUNX1 and RUNX1-ETO: roles in hematopoiesis and leukemogenesis. Lam K, Zhang DE. Front Biosci (Landmark Ed) 17 1120-1139 (2012)
  9. Transcriptional dysregulation during myeloid transformation in AML. Pabst T, Mueller BU. Oncogene 26 6829-6837 (2007)
  10. Protein dynamics and function from solution state NMR spectroscopy. Kovermann M, Rogne P, Wolf-Watz M. Q Rev Biophys 49 e6 (2016)
  11. RUNX1 mutations in clonal myeloid disorders: from conventional cytogenetics to next generation sequencing, a story 40 years in the making. Mangan JK, Speck NA. Crit Rev Oncog 16 77-91 (2011)
  12. Function of CBFbeta/Bro proteins. Adya N, Castilla LH, Liu PP. Semin Cell Dev Biol 11 361-368 (2000)
  13. Normal and transforming functions of RUNX1: a perspective. Mikhail FM, Sinha KK, Saunthararajah Y, Nucifora G. J Cell Physiol 207 582-593 (2006)
  14. Runx3 knockouts and stomach cancer. Levanon D, Brenner O, Otto F, Groner Y. EMBO Rep 4 560-564 (2003)
  15. RUNX family: Oncogenes or tumor suppressors (Review). Otálora-Otálora BA, Henríquez B, López-Kleine L, Rojas A. Oncol Rep 42 3-19 (2019)
  16. Point mutations of the RUNx1/AML1 gene in sporadic and familial myeloid leukemias. Osato M, Yanagida M, Shigesada K, Ito Y. Int J Hematol 74 245-251 (2001)
  17. Transcription factors: global and detailed views. Müller CW. Curr Opin Struct Biol 11 26-32 (2001)
  18. Runx1/AML1 in leukemia: disrupted association with diverse protein partners. Perry C, Eldor A, Soreq H. Leuk Res 26 221-228 (2002)
  19. CBF--a biophysical perspective. Bushweller JH. Semin Cell Dev Biol 11 377-382 (2000)
  20. RUNX1 Dosage in Development and Cancer. Lie-A-Ling M, Mevel R, Patel R, Blyth K, Baena E, Kouskoff V, Lacaud G. Mol Cells 43 126-138 (2020)
  21. Structural and functional characterization of Runx1, CBF beta, and CBF beta-SMMHC. Zhang L, Lukasik SM, Speck NA, Bushweller JH. Blood Cells Mol Dis 30 147-156 (2003)
  22. Transcriptional control of blood cell emergence. Menegatti S, de Kruijf M, Garcia-Alegria E, Lacaud G, Kouskoff V. FEBS Lett 593 3304-3315 (2019)
  23. RUN(X) out of blood: emerging RUNX1 functions beyond hematopoiesis and links to Down syndrome. Rozen EJ, Ozeroff CD, Allen MA. Hum Genomics 17 83 (2023)

Articles citing this publication (35)

  1. Structural analyses of DNA recognition by the AML1/Runx-1 Runt domain and its allosteric control by CBFbeta. Tahirov TH, Inoue-Bungo T, Morii H, Fujikawa A, Sasaki M, Kimura K, Shiina M, Sato K, Kumasaka T, Yamamoto M, Ishii S, Ogata K. Cell 104 755-767 (2001)
  2. Dimerization with PEBP2beta protects RUNX1/AML1 from ubiquitin-proteasome-mediated degradation. Huang G, Shigesada K, Ito K, Wee HJ, Yokomizo T, Ito Y. EMBO J 20 723-733 (2001)
  3. Comparative protein structure modeling by iterative alignment, model building and model assessment. John B, Sali A. Nucleic Acids Res 31 3982-3992 (2003)
  4. Auto-inhibition and partner proteins, core-binding factor beta (CBFbeta) and Ets-1, modulate DNA binding by CBFalpha2 (AML1). Gu TL, Goetz TL, Graves BJ, Speck NA. Mol Cell Biol 20 91-103 (2000)
  5. Functional analysis of RUNX2 mutations in Japanese patients with cleidocranial dysplasia demonstrates novel genotype-phenotype correlations. Yoshida T, Kanegane H, Osato M, Yanagida M, Miyawaki T, Ito Y, Shigesada K. Am J Hum Genet 71 724-738 (2002)
  6. Auto-inhibition of Ets-1 is counteracted by DNA binding cooperativity with core-binding factor alpha2. Goetz TL, Gu TL, Speck NA, Graves BJ. Mol Cell Biol 20 81-90 (2000)
  7. Disease mutations in RUNX1 and RUNX2 create nonfunctional, dominant-negative, or hypomorphic alleles. Matheny CJ, Speck ME, Cushing PR, Zhou Y, Corpora T, Regan M, Newman M, Roudaia L, Speck CL, Gu TL, Griffey SM, Bushweller JH, Speck NA. EMBO J 26 1163-1175 (2007)
  8. Assessment of gene regulation by bone morphogenetic protein 2 in human marrow stromal cells using gene array technology. Locklin RM, Riggs BL, Hicok KC, Horton HF, Byrne MC, Khosla S. J Bone Miner Res 16 2192-2204 (2001)
  9. Multiple mapping method: a novel approach to the sequence-to-structure alignment problem in comparative protein structure modeling. Rai BK, Fiser A. Proteins 63 644-661 (2006)
  10. Mutations of the AML1 gene in acute myeloid leukemia of FAB types M0 and M7. Langabeer SE, Gale RE, Rollinson SJ, Morgan GJ, Linch DC. Genes Chromosomes Cancer 34 24-32 (2002)
  11. MODBASE, a database of annotated comparative protein structure models. Sánchez R, Pieper U, Mirković N, de Bakker PI, Wittenstein E, Sali A. Nucleic Acids Res 28 250-253 (2000)
  12. Oct-1 counteracts autoinhibition of Runx2 DNA binding to form a novel Runx2/Oct-1 complex on the promoter of the mammary gland-specific gene beta-casein. Inman CK, Li N, Shore P. Mol Cell Biol 25 3182-3193 (2005)
  13. 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 UH. J Mol Biol 322 259-272 (2002)
  14. DNA recognition by the RUNX1 transcription factor is mediated by an allosteric transition in the RUNT domain and by DNA bending. Bartfeld D, Shimon L, Couture GC, Rabinovich D, Frolow F, Levanon D, Groner Y, Shakked Z. Structure 10 1395-1407 (2002)
  15. Functional analysis of RUNX2 mutations in cleidocranial dysplasia: novel insights into genotype-phenotype correlations. Yoshida T, Kanegane H, Osato M, Yanagida M, Miyawaki T, Ito Y, Shigesada K. Blood Cells Mol Dis 30 184-193 (2003)
  16. Conservation and expression of an alternative 3' exon of Runx2 encoding a novel proline-rich C-terminal domain. Terry A, Kilbey A, Vaillant F, Stewart M, Jenkins A, Cameron E, Neil JC. Gene 336 115-125 (2004)
  17. Filamin A-bound PEBP2beta/CBFbeta is retained in the cytoplasm and prevented from functioning as a partner of the Runx1 transcription factor. Yoshida N, Ogata T, Tanabe K, Li S, Nakazato M, Kohu K, Takafuta T, Shapiro S, Ohta Y, Satake M, Watanabe T. Mol Cell Biol 25 1003-1012 (2005)
  18. Biophysical characterization of interactions between the core binding factor alpha and beta subunits and DNA. Tang YY, Crute BE, Kelley JJ, Huang X, Yan J, Shi J, Hartman KL, Laue TM, Speck NA, Bushweller JH. FEBS Lett 470 167-172 (2000)
  19. Runx1 binds as a dimeric complex to overlapping Runx1 sites within a palindromic element in the human GM-CSF enhancer. Bowers SR, Calero-Nieto FJ, Valeaux S, Fernandez-Fuentes N, Cockerill PN. Nucleic Acids Res 38 6124-6134 (2010)
  20. Identification of novel CBFA1/RUNX2 mutations causing cleidocranial dysplasia. Bergwitz C, Prochnau A, Mayr B, Kramer FJ, Rittierodt M, Berten HL, Hausamen JE, Brabant G. J Inherit Metab Dis 24 648-656 (2001)
  21. Regulation of RUNX1 dosage is crucial for efficient blood formation from hemogenic endothelium. Lie-A-Ling M, Marinopoulou E, Lilly AJ, Challinor M, Patel R, Lancrin C, Kouskoff V, Lacaud G. Development 145 dev149419 (2018)
  22. AML1B transcriptional repressor function is impaired by the Flt3-internal tandem duplication. Takahashi S, Harigae H, Kameoka J, Sasaki T, Kaku M. Br J Haematol 130 428-436 (2005)
  23. Novel loss-of-function mutations of the haematopoiesis-related transcription factor, acute myeloid leukaemia 1/runt-related transcription factor 1, detected in acute myeloblastic leukaemia and myelodysplastic syndrome. Nakao M, Horiike S, Fukushima-Nakase Y, Nishimura M, Fujita Y, Taniwaki M, Okuda T. Br J Haematol 125 709-719 (2004)
  24. The Runt domain of AML1 (RUNX1) binds a sequence-conserved RNA motif that mimics a DNA element. Fukunaga J, Nomura Y, Tanaka Y, Amano R, Tanaka T, Nakamura Y, Kawai G, Sakamoto T, Kozu T. RNA 19 927-936 (2013)
  25. News Runt domains take the lead in hematopoiesis and osteogenesis. Werner MH, Shigesada K, Ito Y. Nat Med 5 1356-1357 (1999)
  26. Selective base excision repair of DNA damage by the non-base-flipping DNA glycosylase AlkC. Shi R, Mullins EA, Shen XX, Lay KT, Yuen PK, David SS, Rokas A, Eichman BF. EMBO J 37 63-74 (2018)
  27. 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 SM, Liu Y, Grembecka J, Bielnicka I, Bushweller JH, Speck NA. J Mol Biol 364 1073-1083 (2006)
  28. CBFβ and the leukemogenic fusion protein CBFβ-SMMHC associate with mitotic chromosomes to epigenetically regulate ribosomal genes. Lopez-Camacho C, van Wijnen AJ, Lian JB, Stein JL, Stein GS. J Cell Biochem 115 2155-2164 (2014)
  29. Core binding factor β (CBFβ) is retained in the midbody during cytokinesis. Lopez-Camacho C, van Wijnen AJ, Lian JB, Stein JL, Stein GS. J Cell Physiol 229 1466-1474 (2014)
  30. Solution structure of a DNA mimicking motif of an RNA aptamer against transcription factor AML1 Runt domain. Nomura Y, Tanaka Y, Fukunaga J, Fujiwara K, Chiba M, Iibuchi H, Tanaka T, Nakamura Y, Kawai G, Kozu T, Sakamoto T. J Biochem 154 513-519 (2013)
  31. Identification of the regions involved in DNA binding by the mouse PEBP2alpha protein. Pérez-Alvarado GC, Munnerlyn A, Dyson HJ, Grosschedl R, Wright PE. FEBS Lett 470 125-130 (2000)
  32. Chloride binding by the AML1/Runx1 transcription factor studied by NMR. Wolf-Watz M, Bäckström S, Grundström T, Sauer U, Härd T. FEBS Lett 488 81-84 (2001)
  33. Novel Mutation of the RUNX2 Gene in Patients with Cleidocranial Dysplasia. Hordyjewska E, Jaruga A, Kandzierski G, Tylzanowski P. Mol Syndromol 8 253-260 (2017)
  34. Characterisation of an aptamer against the Runt domain of AML1 (RUNX1) by NMR and mutational analyses. Takada K, Amano R, Nomura Y, Tanaka Y, Sugiyama S, Nagata T, Katahira M, Nakamura Y, Kozu T, Sakamoto T. FEBS Open Bio 8 264-270 (2018)
  35. Conjugation of two RNA aptamers improves binding affinity to AML1 Runt domain. Nomura Y, Yamazaki K, Amano R, Takada K, Nagata T, Kobayashi N, Tanaka Y, Fukunaga J, Katahira M, Kozu T, Nakamura Y, Haishima Y, Torigoe H, Sakamoto T. J Biochem 162 431-436 (2017)


Quick links