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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 3004-15 (2000)
Cited: 76 times
EuropePMC logo PMID: 10856244

Abstract

Mutations in the genes encoding the interacting proteins AML1 and CBFbeta are the most common genetic abnormalities in acute leukaemia, and congenital mutations in the related AML3 gene are associated with disorders of osteogenesis. Furthermore, the interaction of AML1 with CBFbeta is essential for haematopoiesis. We report the 2.6 A resolution crystal structure of the complex between the AML1 Runt domain and CBFbeta, which represents a paradigm for the mode of interaction of this highly conserved family of transcription factors. The structure demonstrates that point mutations associated with cleidocranial dysplasia map to the conserved heterodimer interface, suggesting a role for CBFbeta in osteogenesis, and reveals a potential protein interaction platform composed of conserved negatively charged residues on the surface of CBFbeta.

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  1. CBFβ stabilizes HIV Vif to counteract APOBEC3 at the expense of RUNX1 target gene expression. Kim DY, Kwon E, Hartley PD, Crosby DC, Mann S, Krogan NJ, Gross JD. Mol. Cell 49 632-644 (2013)
  2. MuPIT interactive: webserver for mapping variant positions to annotated, interactive 3D structures. Niknafs N, Kim D, Kim R, Diekhans M, Ryan M, Stenson PD, Cooper DN, Karchin R. Hum. Genet. 132 1235-1243 (2013)
  3. PI2PE: protein interface/interior prediction engine. Tjong H, Qin S, Zhou HX. Nucleic Acids Res. 35 W357-62 (2007)
  4. Relating destabilizing regions to known functional sites in proteins. Dessailly BH, Lensink MF, Wodak SJ. BMC Bioinformatics 8 141 (2007)
  5. Topology independent protein structural alignment. Dundas J, Binkowski TA, DasGupta B, Liang J. BMC Bioinformatics 8 388 (2007)
  6. Small Molecule Inhibitor of CBFβ-RUNX Binding for RUNX Transcription Factor Driven Cancers. Illendula A, Gilmour J, Grembecka J, Tirumala VSS, Boulton A, Kuntimaddi A, Schmidt C, Wang L, Pulikkan JA, Zong H, Parlak M, Kuscu C, Pickin A, Zhou Y, Gao Y, Mishra L, Adli M, Castilla LH, Rajewski RA, Janes KA, Guzman ML, Bonifer C, Bushweller JH. EBioMedicine 8 117-131 (2016)
  7. Genetic basis for iMCD-TAFRO. Yoshimi A, Trippett TM, Zhang N, Chen X, Penson AV, Arcila ME, Pichardo J, Baik J, Sigler A, Harada H, Fajgenbaum DC, Dogan A, Abdel-Wahab O, Xiao W. Oncogene 39 3218-3225 (2020)
  8. PI2PE: A Suite of Web Servers for Predictions Ranging From Protein Structure to Binding Kinetics. Qin S, Zhou HX. Biophys Rev 5 41-46 (2013)
  9. Comparative analysis of web-based programs for single amino acid substitutions in proteins. Choudhury A, Mohammad T, Anjum F, Shafie A, Singh IK, Abdullaev B, Pasupuleti VR, Adnan M, Yadav DK, Hassan MI. PLoS One 17 e0267084 (2022)
  10. 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)
  11. RUNX3 inactivates oncogenic MYC through disruption of MYC/MAX complex and subsequent recruitment of GSK3β-FBXW7 cascade. Oei V, Chuang LSH, Matsuo J, Srivastava S, Teh M, Ito Y. Commun Biol 6 689 (2023)


Reviews citing this publication (21)

  1. Oncogenic potential of the RUNX gene family: 'overview'. Ito Y. Oncogene 23 4198-4208 (2004)
  2. Runx2: a master organizer of gene transcription in developing and maturing osteoblasts. Schroeder TM, Jensen ED, Westendorf JJ. Birth Defects Res. C Embryo Today 75 213-225 (2005)
  3. Mutations in the RUNX2 gene in patients with cleidocranial dysplasia. Otto F, Kanegane H, Mundlos S. Hum. Mutat. 19 209-216 (2002)
  4. AML1 and the AML1-ETO fusion protein in the pathogenesis of t(8;21) AML. Licht JD. Oncogene 20 5660-5679 (2001)
  5. RUNX1 and RUNX1-ETO: roles in hematopoiesis and leukemogenesis. Lam K, Zhang DE. Front Biosci (Landmark Ed) 17 1120-1139 (2012)
  6. Mechanism of leukemogenesis by the inv(16) chimeric gene CBFB/PEBP2B-MHY11. Shigesada K, van de Sluis B, Liu PP. Oncogene 23 4297-4307 (2004)
  7. Normal and transforming functions of RUNX1: a perspective. Mikhail FM, Sinha KK, Saunthararajah Y, Nucifora G. J. Cell. Physiol. 207 582-593 (2006)
  8. FOXP3 and its partners: structural and biochemical insights into the regulation of FOXP3 activity. Zhou Z, Song X, Li B, Greene MI. Immunol. Res. 42 19-28 (2008)
  9. Familial mutations of the transcription factor RUNX1 (AML1, CBFA2) predispose to acute myeloid leukemia. Ganly P, Walker LC, Morris CM. Leuk. Lymphoma 45 1-10 (2004)
  10. Transcription factors: global and detailed views. Müller CW. Curr. Opin. Struct. Biol. 11 26-32 (2001)
  11. Eukaryotic transcription factors. Warren AJ. Curr. Opin. Struct. Biol. 12 107-114 (2002)
  12. Targeting protein-protein interactions in hematologic malignancies: still a challenge or a great opportunity for future therapies? Cierpicki T, Grembecka J. Immunol. Rev. 263 279-301 (2015)
  13. Function of the inv(16) fusion gene CBFB-MYH11. Kundu M, Liu PP. Curr. Opin. Hematol. 8 201-205 (2001)
  14. 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)
  15. CBF--a biophysical perspective. Bushweller JH. Semin. Cell Dev. Biol. 11 377-382 (2000)
  16. Targeting binding partners of the CBFβ-SMMHC fusion protein for the treatment of inversion 16 acute myeloid leukemia. Richter L, Wang Y, Hyde RK. Oncotarget 7 66255-66266 (2016)
  17. Genetic compensation of RUNX family transcription factors in leukemia. Kamikubo Y. Cancer Sci. 109 2358-2363 (2018)
  18. CROX (Cluster Regulation of RUNX) as a Potential Novel Therapeutic Approach. Kamikubo Y. Mol Cells 43 198-202 (2020)
  19. Core Binding Factor Leukemia: Chromatin Remodeling Moves Towards Oncogenic Transcription. Beghini A. Cancers (Basel) 11 (2019)
  20. Intracellular Antibodies for Drug Discovery and as Drugs of the Future. Rabbitts TH. Antibodies (Basel) 12 24 (2023)
  21. Overview of protein structural and functional folds. Sun PD, Foster CE, Boyington JC. Curr Protoc Protein Sci Chapter 17 Unit 17.1 (2004)

Articles citing this publication (43)

  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. Cbfbeta interacts with Runx2 and has a critical role in bone development. Kundu M, Javed A, Jeon JP, Horner A, Shum L, Eckhaus M, Muenke M, Lian JB, Yang Y, Nuckolls GH, Stein GS, Liu PP. Nat. Genet. 32 639-644 (2002)
  4. The RUNX3 gene--sequence, structure and regulated expression. Bangsow C, Rubins N, Glusman G, Bernstein Y, Negreanu V, Goldenberg D, Lotem J, Ben-Asher E, Lancet D, Levanon D, Groner Y. Gene 279 221-232 (2001)
  5. Structural basis for hijacking CBF-β and CUL5 E3 ligase complex by HIV-1 Vif. Guo Y, Dong L, Qiu X, Wang Y, Zhang B, Liu H, Yu Y, Zang Y, Yang M, Huang Z. Nature 505 229-233 (2014)
  6. Architecture and anatomy of the genomic locus encoding the human leukemia-associated transcription factor RUNX1/AML1. Levanon D, Glusman G, Bangsow T, Ben-Asher E, Male DA, Avidan N, Bangsow C, Hattori M, Taylor TD, Taudien S, Blechschmidt K, Shimizu N, Rosenthal A, Sakaki Y, Lancet D, Groner Y. Gene 262 23-33 (2001)
  7. 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)
  8. 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)
  9. Transforming activity of AML1-ETO is independent of CBFbeta and ETO interaction but requires formation of homo-oligomeric complexes. Kwok C, Zeisig BB, Qiu J, Dong S, So CW. Proc. Natl. Acad. Sci. U.S.A. 106 2853-2858 (2009)
  10. CBFbeta allosterically regulates the Runx1 Runt domain via a dynamic conformational equilibrium. Yan J, Liu Y, Lukasik SM, Speck NA, Bushweller JH. Nat. Struct. Mol. Biol. 11 901-906 (2004)
  11. 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)
  12. 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)
  13. 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)
  14. AML1/RUNX1 mutations are infrequent, but related to AML-M0, acquired trisomy 21, and leukemic transformation in pediatric hematologic malignancies. Taketani T, Taki T, Takita J, Tsuchida M, Hanada R, Hongo T, Kaneko T, Manabe A, Ida K, Hayashi Y. Genes Chromosomes Cancer 38 1-7 (2003)
  15. 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)
  16. Accelerated leukemogenesis by truncated CBF beta-SMMHC defective in high-affinity binding with RUNX1. Kamikubo Y, Zhao L, Wunderlich M, Corpora T, Hyde RK, Paul TA, Kundu M, Garrett L, Compton S, Huang G, Wolff L, Ito Y, Bushweller J, Mulloy JC, Liu PP. Cancer Cell 17 455-468 (2010)
  17. The role of periodontal ligament cells in delayed tooth eruption in patients with cleidocranial dysostosis. Lossdörfer S, Abou Jamra B, Rath-Deschner B, Götz W, Abou Jamra R, Braumann B, Jäger A. J Orofac Orthop 70 495-510 (2009)
  18. 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)
  19. A RUNX2-Mediated Epigenetic Regulation of the Survival of p53 Defective Cancer Cells. Shin MH, He Y, Marrogi E, Piperdi S, Ren L, Khanna C, Gorlick R, Liu C, Huang J. PLoS Genet. 12 e1005884 (2016)
  20. Characterization of RNA aptamers that disrupt the RUNX1-CBFbeta/DNA complex. Barton JL, Bunka DH, Knowling SE, Lefevre P, Warren AJ, Bonifer C, Stockley PG. Nucleic Acids Res. 37 6818-6830 (2009)
  21. Genetic regulation of the RUNX transcription factor family has antitumor effects. Morita K, Suzuki K, Maeda S, Matsuo A, Mitsuda Y, Tokushige C, Kashiwazaki G, Taniguchi J, Maeda R, Noura M, Hirata M, Kataoka T, Yano A, Yamada Y, Kiyose H, Tokumasu M, Matsuo H, Tanaka S, Okuno Y, Muto M, Naka K, Ito K, Kitamura T, Kaneda Y, Liu PP, Bando T, Adachi S, Sugiyama H, Kamikubo Y. J. Clin. Invest. 127 2815-2828 (2017)
  22. Regulation of RUNX2 transcription factor-DNA interactions and cell proliferation by vitamin D3 (cholecalciferol) prohormone activity. Underwood KF, D'Souza DR, Mochin-Peters M, Pierce AD, Kommineni S, Choe M, Bennett J, Gnatt A, Habtemariam B, MacKerell AD, Passaniti A. J. Bone Miner. Res. 27 913-925 (2012)
  23. 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)
  24. CBFB-MYH11 hinders early T-cell development and induces massive cell death in the thymus. Zhao L, Cannons JL, Anderson S, Kirby M, Xu L, Castilla LH, Schwartzberg PL, Bosselut R, Liu PP. Blood 109 3432-3440 (2007)
  25. Cbf beta is involved in maturation of all lineages of hematopoietic cells during embryogenesis except erythroid. Kundu M, Liu PP. Blood Cells Mol. Dis. 30 164-169 (2003)
  26. Identification of a new pebp2alphaA2 isoform from zebrafish runx2 capable of inducing osteocalcin gene expression in vitro. Pinto JP, Conceição NM, Viegas CS, Leite RB, Hurst LD, Kelsh RN, Cancela ML. J. Bone Miner. Res. 20 1440-1453 (2005)
  27. Cooperative binding of DNA and CBFbeta to the Runt domain of the CBFalpha studied via MD simulations. Habtemariam B, Anisimov VM, MacKerell AD. Nucleic Acids Res. 33 4212-4222 (2005)
  28. Runx transcription factors repress human and murine c-Myc expression in a DNA-binding and C-terminally dependent manner. Jacobs PT, Cao L, Samon JB, Kane CA, Hedblom EE, Bowcock A, Telfer JC. PLoS ONE 8 e69083 (2013)
  29. A DNA-binding-independent pathway of repression by the Drosophila Runt protein. Vander Zwan CJ, Wheeler JC, Li LH, Tracey WD, Gergen JP. Blood Cells Mol. Dis. 30 207-222 (2003)
  30. A novel in-frame deletion of the RUNX2 gene causes a classic form of cleidocranial dysplasia. Matsushita M, Kitoh H, Kaneko H, Mishima K, Itoh Y, Tokita Y, Ishiguro N. J. Bone Miner. Metab. 32 96-99 (2014)
  31. The HMG-box protein Lilliputian is required for Runt-dependent activation of the pair-rule gene fushi-tarazu. Vanderzwan-Butler CJ, Prazak LM, Gergen JP. Dev. Biol. 301 350-360 (2007)
  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. RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemia. Matthijssens F, Sharma ND, Nysus M, Nickl CK, Kang H, Perez DR, Lintermans B, Van Loocke W, Roels J, Peirs S, Demoen L, Pieters T, Reunes L, Lammens T, De Moerloose B, Van Nieuwerburgh F, Deforce DL, Cheung LC, Kotecha RS, Risseeuw MD, Van Calenbergh S, Takarada T, Yoneda Y, van Delft FW, Lock RB, Merkley SD, Chigaev A, Sklar LA, Mullighan CG, Loh ML, Winter SS, Hunger SP, Goossens S, Castillo EF, Ornatowski W, Van Vlierberghe P, Matlawska-Wasowska K. J Clin Invest 131 141566 (2021)
  34. AML1 and AML1 fusion protein AML1-ETO in myeloid gene regulation and leukemogenesis. Zhang DE, Burel S, Zhou L, Hetherington CJ, Yuan Y. Blood Cells Mol. Dis. 27 368-376 (2001)
  35. Autonomous feedback loop of RUNX1-p53-CBFB in acute myeloid leukemia cells. Morita K, Noura M, Tokushige C, Maeda S, Kiyose H, Kashiwazaki G, Taniguchi J, Bando T, Yoshida K, Ozaki T, Matsuo H, Ogawa S, Liu PP, Nakahata T, Sugiyama H, Adachi S, Kamikubo Y. Sci Rep 7 16604 (2017)
  36. HDAC1 Is a Required Cofactor of CBFβ-SMMHC and a Potential Therapeutic Target in Inversion 16 Acute Myeloid Leukemia. Richter LE, Wang Y, Becker ME, Coburn RA, Williams JT, Amador C, Hyde RK. Mol Cancer Res 17 1241-1252 (2019)
  37. Transcriptional regulation of gilthead seabream bone morphogenetic protein (BMP) 2 gene by bone- and cartilage-related transcription factors. Marques CL, Cancela ML, Laizé V. Gene 576 229-236 (2016)
  38. Interactions between lineage-associated transcription factors govern haematopoietic progenitor states. Kucinski I, Wilson NK, Hannah R, Kinston SJ, Cauchy P, Lenaerts A, Grosschedl R, Göttgens B. EMBO J 39 e104983 (2020)
  39. RUN-CBFbeta interaction in C. elegans: computational prediction and experimental verification. Suad O, Eyal E, Blumenzweig I, Kessler N, Levanon D, Groner Y, Shakked Z. J. Biomol. Struct. Dyn. 24 343-358 (2007)
  40. Clinicopathological Significance of RUNX1 in Non-Small Cell Lung Cancer. Kim Y, Lee BB, Kim D, Um S, Cho EY, Han J, Shim YM, Kim DH. J Clin Med 9 (2020)
  41. PmRunt regulated by Pm-miR-183 participates in nacre formation possibly through promoting the expression of collagen VI-like and Nacrein in pearl oyster Pinctada martensii. Zheng Z, Du X, Xiong X, Jiao Y, Deng Y, Wang Q, Huang R. PLoS ONE 12 e0178561 (2017)
  42. RUNX family: Oncogenes or tumor suppressors (Review). Otálora-Otálora BA, Henríquez B, López-Kleine L, Rojas A. Oncol. Rep. 42 3-19 (2019)
  43. RUNX1 inhibits proliferation and induces apoptosis of t(8;21) leukemia cells via KLF4-mediated transactivation of P57. Liu S, Xing Y, Lu W, Li S, Tian Z, Xing H, Tang K, Xu Y, Rao Q, Wang M, Wang J. Haematologica 104 1597-1607 (2019)


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