Conformational flexibility of the oncogenic protein LMO2 primes the formation of the multi-protein transcription complex

Scientific Reports

Volumn 4, Issue , 2014, Pages

  Sewell, H ^a,b,d   Tanaka, T ^b,e   Omari, K El ^c   Mancini, E J ^c   Cruz, A ^a,b   Fernandez Fuentes, N ^b,f   Chambers, J ^a,b   Rabbitts, T H ^a,b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b ST JAMES S UNIVERSITY HOSPITAL   (United Kingdom)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d Fujifilm Diosynth Biotechnologies   (United Kingdom)

^e DAINIPPON SUMITOMO PHARMA CO LTD   (Japan)

^f ABERYSTWYTH UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

LIM PROTEIN; LMO2 PROTEIN, HUMAN; ONCOPROTEIN; SIGNAL TRANSDUCING ADAPTOR PROTEIN;

ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; CRYSTALLIZATION; GENETIC TRANSCRIPTION; GENETICS; MUTATION; PROTEIN BINDING; PROTEIN CONFORMATION; X RAY CRYSTALLOGRAPHY;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; CRYSTALLIZATION; CRYSTALLOGRAPHY, X-RAY; LIM DOMAIN PROTEINS; MODELS, MOLECULAR; MUTATION; PROTEIN BINDING; PROTEIN CONFORMATION; PROTO-ONCOGENE PROTEINS; TRANSCRIPTION, GENETIC;

EID: 84892184111     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep03643     Document Type: Article

References (74)

1. Rabbitts, T. H. Chromosomal translocation master genes, mouse models and experimental therapeutics. Oncogene 20, 5763-77 (2001). (Pubitemid 32928114)
2. Boehm, T. et al. The mechanism of chromosomal translocation t(11;14) involving the T-cell receptor Cd locus on human chromosome 14q11 and a transcribed region of chromosome 11p15. EMBO J. 7, 385-394 (1988).
3. Boehm, T., Foroni, L., Kaneko, Y., Perutz, M. P. amp; Rabbitts, T. H. The rhombotin family of cysteine-rich LIM-domain oncogenes: Distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13. Proc. Natl. Acad. Sci. USA 88, 4367-4371 (1991). (Pubitemid 21914541)
4. McGuire, E. A. et al. The t(11;14)(p15;q11) in a T-cell acute lymphoblastic leukemia cell line activates multiple transcripts, including Ttg-1, a gene encoding a potential zinc finger protein. Mol. Cel. Biol. 9, 2124-2132 (1989). (Pubitemid 19117813)
5. Royer-Pokora, B., Loos, U. amp; Ludwig, W.-D. TTG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukaemia with the t(11;14)(p13;q11). Oncogene 6, 1887-1893 (1991). (Pubitemid 21924023)
6. Uebelhart, B. amp; Rizzoli, R. [Osteoporosis and anti-androgenic therapy in case of prostate cancer]. Revue Med Suisse 1, 2261-2, 2264-5 (2005).
7. Simonis, M. et al. High-resolution identification of balanced and complex chromosomal rearrangements by 4C technology. Nature Meth. 6, 837-42 (2009).
8. Natkunam, Y. et al. LMO2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with anthracycline-based chemotherapy with and without rituximab. J Clin Oncol 26, 447-54 (2008). (Pubitemid 351171698)
9. Natkunam, Y. et al. The oncoprotein LMO2 is expressed in normal germinalcenter B cells and in human B-cell lymphomas. Blood 109, 1636-42 (2007). (Pubitemid 46239598)
10. Rizzo, S., Attard, G. amp; Hudson, D. L. Prostate epithelial stem cells. Cell Prolif. 38, 363-74 (2005). (Pubitemid 41746369)
11. Ma, S. et al. The significance of LMO2 expression in the progression of prostate cancer. J. Pathology 211, 278-85 (2007). (Pubitemid 46172703)
12. Wang, K. et al. Integrative genomics identifies LMO1 as a neuroblastoma oncogene. Nature 469, 216-20 (2011).
13. Isogai, E. et al. Oncogenic LMO3 collaborates with HEN2 to enhance neuroblastoma cell growth through transactivation of Mash1. PLoS One 6, e19297 (2011).
14. Aoyama, M. et al. LMO3 interacts with neuronal transcription factor, HEN2, and acts as an oncogene in neuroblastoma. Cancer Res. 65, 4587-97 (2005). (Pubitemid 40740794)
15. Visvader, J. E. et al. The LIM domain gene LMO4 inhibits differentiation of mammary epithelial cells in vitro and is overexpressed in breast cancer. Proc. Natl. Acad. Sci USA 98, 14452-7 (2001). (Pubitemid 33121412)
16. Fisch, P. et al. T-cell acute lymphoblastic lymphoma induced in transgenicmice by the RBTN1 and RBTN2 LIM-domain genes. Oncogene 7, 2389-2397 (1992).
17. Larson, R. et al. T cell tumours with disparate phenotypes develop with long latency in mice transgenic for rbtn2. Oncogene 9, 3675-3681 (1994). (Pubitemid 24359406)
18. Larson, R. C. et al. Protein dimerisation between Lmo2 (Rbtn2) and Tal1 alters thymocyte development and potentiates T cell tumorigenesis in transgenic mice. EMBO J. 15, 1021-1027 (1996). (Pubitemid 26077830)
19. Warren, A. J. et al. The oncogenic cysteine-rich LIM domain protein rbtn2 is essential for erythroid development. Cell 78, 45-58 (1994).
20. Yamada, Y. et al. The T cell leukaemia LIM protein Lmo2 is necessary for adult mouse haematopoiesis. Proc. Natl. Acad. Sci. USA 95, 3890-3895 (1998). (Pubitemid 28173224)
21. Yamada, Y., Pannell, R. amp; Rabbitts, T. H. The oncogenic LIM-only transcription factor Lmo2 regulates angiogenesis but not vasculogenesis. Proc. Natl. Acad. Sci. USA 97, 320-324 (2000). (Pubitemid 30055829)
22. Archer, V. E. et al. Cysteine-rich LIM domains of LIM-homeodomain and LIMonly proteins contain zinc but not iron. Proc. Natl. Acad. Sci. USA a 91, 316-20 (1994). (Pubitemid 24018695)
23. Wadman, I. A. et al. The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA-1 and Ldb1/NLI proteins. EMBO J. 16, 3145-3157 (1997). (Pubitemid 27234954)
24. Herblot, S., Steff, A. M., Hugo, P., Aplan, P. D. amp; Hoang, T. SCL and LMO1 alter thymocyte differentiation: inhibition of E2A-HEB function and pre-T alpha chain expression. Nature Imm. 1, 138-44 (2000).
25. McCormack, M. P., Forster, A., Drynan, L. F., Pannell, R. amp; Rabbitts, T. H. The LMO2 T-cell oncogene is activated via chromosomal translocations or retroviral insertion during gene therapy but has no mandatory role in normal T-cell development. Mol Cell Biol 23, 9003-9013 (2003). (Pubitemid 37499791)
26. Larson, R. C., Osada, H., Larson, T. A., Lavenir, I. amp; Rabbitts, T. H. The oncogenic LIM protein Rbtn2 causes thymic developmental aberrations that precede malignancy in transgenic mice. Oncogene 11, 853-862 (1995).
27. McCormack, M. P. et al. The Lmo2 oncogene initiates leukemia in mice by inducing thymocyte self-renewal. Science 327, 879-83 (2010).
28. Appert, A. et al. Targeting LMO2 with a peptide aptamer establishes a necessary function in overt T-cell neoplasia. Cancer Res 69, 4784-90 (2009).
29. Nam, C. H. et al. An antibody inhibitor of the LMO2-protein complex blocks its normal and tumorigenic functions. Oncogene 27, 4962-8 (2008).
30. Kadrmas, J. L. amp; Beckerle, M. C. The LIM domain: from the cytoskeleton to the nucleus. Nature Rev. Mol Cell Biol. 5, 920-31 (2004). (Pubitemid 39486543)
31. Wright, W. E. amp; Funk, W. D. CASTing for multicomponent DNA-binding complexes. TIBS 18, 77-80 (1993). (Pubitemid 23080694)
32. Grutz, G. et al. The oncogenic T cell LIM-protein Lmo2 forms part of a DNAbinding complex specifically in immature T cells. EMBO J. 17, 4594-4605 (1998). (Pubitemid 28377160)
33. Wadman, I. et al. Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. EMBO J 13, 4831-9 (1994). (Pubitemid 24319365)
34. Meng, Y. S., Khoury, H., Dick, J. E. amp; Minden, M. D. Oncogenic potential of the transcription factor LYL1 in acute myeloblastic leukemia. Leukemia 19, 1941-7 (2005). (Pubitemid 41554003)
35. Tanaka, T., Sewell, H., Waters, S., Philips, S. amp; Rabbitts, T. H. Single domain intracellular antibodies from diverse libraries:emphasizing dual functions of LMO2 protein interactions using a VH single domian. J Biol Chem 286, 3707-3716 (2010).
36. El Omari, K. et al. Structure of the leukemia oncogene LMO2: implications for the assembly of a hematopoietic transcription factor complex. Blood 117, 2146-56 (2011).
37. Tse, E. et al. Intracellular antibody capture technology: application to selection of single chain Fv recognising the BCR-ABL oncogenic protein. J. Mol. Biol. 317, 85-94 (2002). (Pubitemid 34722201)
38. Tanaka, T. amp; Rabbitts, T. H. Protocol for the selection of single-domain antibody fragments by third generation intracellular antibody capture. Nature Protocols 5, 67-92 (2010).
39. McCall, K. A., Huang, C. amp; Fierke, C. A. Function and mechanism of zinc metalloenzymes. J. Nutr. 130, 1437S-46S (2000). (Pubitemid 30244143)
40. Yang, Z. R., Thomson, R., McNeil, P. amp; Esnouf, R. M. RONN: the bio-basis function neural network technique applied to the detection of natively disordered regions in proteins. Bioinformatics 21, 3369-76 (2005). (Pubitemid 41222441)
41. Sickmeier, M. et al. DisProt: the Database of Disordered Proteins. Nucleic Acids Res 35, D786-93 (2007). (Pubitemid 46056310)
42. Sanchez-Garcia, I., Axelson, H. amp; Rabbitts, T. H. Functional diversity of LIM proteins: amino-terminal activation domains in the oncogenic proteins RBTN1 and RBTN2. Oncogene 10, 1301-1306 (1995).
43. Deane, J. E. et al. Tandem LIM domains provide synergistic binding in the LMO4:Ldb1 complex. EMBO J. 23, 3589-98 (2004). (Pubitemid 39336281)
44. Matthews, J. M., Visvader, J. E. amp; Mackay, J. P. 1H, 15N and 13C assignments of FLIN2, an intramolecular LMO2:ldb1 complex. J. Biomol. NMR21, 385-6 (2001).
45. Ryan, D. P. et al. Identification of the key LMO2-binding determinants on Ldb1. J Mol Biol 359, 66-75 (2006).
46. Rabbitts, T. H. Translocations, Master genes, and Differences between the Origins of Acute and Chronic Leukemias. Cell 67, 641-644 (1991). (Pubitemid 121001477)
47. Xu, Z. et al. Single-stranded DNA-binding proteins regulate the abundance of LIM domain and LIM domain-binding proteins. Genes amp; Devel. 21, 942-55 (2007). (Pubitemid 46625643)
48. Stewart, M. Molecular mechanism of the nuclear protein import cycle. Nat Rev Mol Cell Biol 8, 195-208 (2007).
49. Dastmalchi, S. et al. Solution structure of a tethered Lmo2(LIM2)/Ldb1(LID) complex. Protein Sci 21, 1768-74 (2012).
50. Osada, H., Grutz, G., Axelson, H., Forster, A. amp; Rabbitts, T. H. Association of erythroid transcription factors: Complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1. Proc. Natl. Acad. Sci. USA 92, 9585-9589 (1995).
51. Wilkinson-White, L. et al. Structural basis of simultaneous recruitment of the transcriptional regulators LMO2 and FOG1/ZFPM1 by the transcription factor GATA1. Proc Natl Acad Sci USA 108, 14443-8 (2011).
52. Flores, S. C., Lu, L. J., Yang, J., Carriero, N. amp; Gerstein, M. B. Hinge Atlas: relating protein sequence to sites of structural flexibility. BMC Bioinformatics 8, 167 (2007).
53. Perez-Martinez, D., Tanaka, T. amp; Rabbitts, T. H. Intracellular antibodies and cancer: new technologies offer therapeutic opportunities. BioEssays 32, 589-98 (2010).
54. Forster, A. et al. Chromosomal translocation engineering to recapitulate primary events of human cancer. Cold Spring Harb Symp Quant Biol 70, 275-82 (2005). (Pubitemid 44124881)
55. Wells, J. A. McClendon, C. L. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature 450, 1001-9 (2007). (Pubitemid 350273630)
56. Congreve, M., Chessari, G., Tisi, D. amp; Woodhead, A. J. Recent developments in fragment-based drug discovery. J. Med. Chem 51, 3661-80 (2008). (Pubitemid 351956496)
57. Otwinowski, Z. amp; Minor, W. Porcessing of X-fay diffraction data collected in oscillation mode. Methods Ezymol 276 (1997).
58. Matthews, B. W. Solvent content of protein crystals. J Mol Biol 33, 491-7 (1968).
59. McCoy, A. J. et al. Phaser crystallographic software. J. Appl Cryst 40, 658-674 (2007). (Pubitemid 47080256)
60. Adams, P. D. et al. The Phenix software for automated determination of macromolecular structures. Methods 55, 94-106 (2011).
61. Vagin, A. amp; Teplyakov, A. Molecular replacement with MOLREP. Acta Crystallogr D Biol Crystallogr 66, 22-5 (2010).
62. Emsley, P. amp; Cowtan, K. Coot: model-building tools for molecular graphics. Acta Cryst 60, 2126-32 (2004). (Pubitemid 41742764)
63. Blanc, E. et al. Refinement of severely incomplete structures with maximum likelihood in BUSTER-TNT. Acta Cryst 60, 2210-21 (2004). (Pubitemid 41742773)
64. Murshudov, G. N., Vagin, A. A. amp; Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Cryst 53, 240-55 (1997). (Pubitemid 27235885)
65. Tanaka, T., Lobato, M. N.Rabbitts, T. H. Single domain intracellular antibodies: a minimal fragment for direct in vivo selection of antigen-specific intrabodies. J. Mol. Biol. 331, 1109-1120 (2003). (Pubitemid 36969968)
66. Sadowski, I., Bell, B., Broad, P. amp; Hollis, M. GAL4 fusion vectors for expression in yeast or mammalian cells. Gene 118, 137-141 (1992).
67. Tanaka, T. amp; Rabbitts, T. H. Intrabodies based on intracellular capture frameworks that bind the RAS protein with high affinity and impair oncogenic transformation. EMBO J 22, 1025-1035 (2003). (Pubitemid 36313587)
68. Lois, C., Hong, E. J., Pease, S., Brown, E. J. amp; Baltimore, D. Germline transmission and tissue-specific expression of transgenes delivered by lentiviral vectors. Science 295, 868-72 (2002). (Pubitemid 34118370)
69. Cornell, W. D. et al. A second generation force field for the simulation of proteins, nucleic acids and organic molecules. J. Am. Chem. Soc 117, 5179-5197 (1995).
70. Fernandez-Fuentes, N., Rai, B. K., Madrid-Aliste, C. J., Fajardo, J. E. amp; Fiser, A. Comparative protein structure modeling by combining multiple templates and optimizing sequence-to-structure alignments. Bioinformatics 23, 2558-65 (2007). (Pubitemid 350048358)
71. Omichinski, J. G. et al. NMR structure of a specific DNA complex of Zncontaining DNA binding domain of GATA-1. Science 261, 438-46 (1993). (Pubitemid 23276551)
72. Kowalski, K., Czolij, R., King, G. F., Crossley, M. amp; Mackay, J. P. The solution structure of the N-terminal zinc finger of GATA-1 reveals a specific binding face for the transcriptional co-factor FOG. J Biomol NMR 13, 249-62 (1999). (Pubitemid 29143532)
73. Longo, A., Guanga, G. P. amp; Rose, R. B. Crystal structure of E47-NeuroD1/beta2 bHLH domain-DNA complex: heterodimer selectivity and DNA recognition. Biochemistry 47, 218-29 (2008).
74. Wilkinson-White, L. et al. Structural basis of simultaneous recruitment of the transcriptional regulators LMO2 and FOG1/ZFPM1 by the transcription factor GATA1. Proc. Natl Acad Sci USA 108, 14443-8 (2011).