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A novel post-transcriptional splicing form of the acute T cell leukemia proto-oncogeneLmo2

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Abstract

Lmo2 is a T cell leukemia-related proto-oncogene, which belongs to the LIM protein family. Previous work has established its key role in yolk sac erythropoiesis and adult hematopoiesis, and it is also necessary for regulating angiogenesis. It has been demonstrated that this gene encodes a protein of 158 amino acids, consisting of two tandem cysteine-rich LIM domains, but the detailed mechanism of its transcriptional regulation remains to be elucidated. To further investigate the mechanism of transcriptional regulation ofLmo2, we combined SMART PCR technology with 5′RACE and found a novel post-transcriptional splicing form ofLmo2 in adult human kidney. This alternative transcript contains only two exons, encoding a smaller protein of 151 amino acids. Interestingly, it shares the same reading frame as the originalLmo2, but differs in 7 amino acids at the N-terminus. Agenomic DNA fragment (from −294 nts to +180 nts) containing the putative promoter region has been inserted into the luciferase reporter gene vector pGL3-basic and showed stable promoter activity when transfected into COS7. RT-PCR analysis revealed that this variant transcript was expressed widely in human tissues and cell lines, suggesting its potential basic functional importance.

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References

  1. Feuerstein, R., Wang, X., Song, D. et al., The LIM/double zinc-finger motif: A novel protein dimerization domain, Proc. Natl. Acad. Sci. USA, 1994, 91: 10655–10659.

    Article  PubMed  CAS  Google Scholar 

  2. Schmeichel, K. L., Beckerle, M. C., The LIM domain is a modular protein-binding interface, Cell, 1994, 79: 211–219.

    Article  PubMed  CAS  Google Scholar 

  3. Boehm, T., Foroni, L., Kaneko, Y. et al., The rhombotin family of cystein-rich LIM-domain oncogenes: distinct members are involved in T-cell translocations to human chromosome 11p15 and 11p13, Pro. Natl. Acad. Sci. USA, 1991, 88: 4367–4371.

    Article  CAS  Google Scholar 

  4. Royer-Pokora, B., Uschi, L., Ludwig, W. D. et al., TTG-2, a new gene encoding a cysteine-rich protein with LIM motif, is overexpressed in acute T-cell leukaemia with the t(11;14)(p13;q11), Oncogene, 1991, 6: 1887–1893.

    PubMed  CAS  Google Scholar 

  5. Warren, A. J., Colledge, W. H., Carlton, M. B. et al., The oncogenic cysteine-rich LIM domain protein Rbtn2 is essential for erythroid development, Cell, 1994, 78: 45–57.

    Article  PubMed  CAS  Google Scholar 

  6. Visvader, J. E., Mao, X. H., Fujuwara, Y. et al., The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation, Pro. Natl. Acad. Sci. USA, 1997, 94: 13707–13712.

    Article  CAS  Google Scholar 

  7. Yamada, Y., Warren, A. J., Dobson, C. et al., The T cell leukemia LIM protein Lmo2 is necessary for adult mouse hematopoiesis, Pro. Natl. Acad. Sci. USA, 1998, 95: 3890–3895.

    Article  CAS  Google Scholar 

  8. Yamada, Y., Pannell, R., Alan, F. et al., The oncogenic LIM-only transcription factor Lmo2 regulates angiogenesis but not vasculogenesis in mice, Proc. Natl. Acad. Sci. USA, 2000, 97: 320–324.

    Article  PubMed  CAS  Google Scholar 

  9. Royer-Pokora, B., Rogers, M., Zhu, T. H. et al., The TTG-2/RBTN-2 T cell oncogene encodes two alternative transcripts from two promoters: the distal promoter is removed by most 11p 13 translocations in acute T cell leukaemia’s (T-ALL), Oncogene, 1995, 10: 1353–1360.

    PubMed  CAS  Google Scholar 

  10. Carninci, P., Nishiyama, Y., Westover, A. et al., Thermostabilization and thermo-activation of thermolabile enzymes by trehalose and its application for the synthesis of full length cDNA, Proc. Natl. Acad. Sci. USA, 1998, 95(1): 520–552.

    Article  PubMed  CAS  Google Scholar 

  11. Look, A. T., Oncogenic transcription factors in the human acute leukemias, Science, 1997, 278: 1059–1064.

    Article  PubMed  CAS  Google Scholar 

  12. Fitzgerald, T. J., Neale, G. A. M., Raimondi, S. C. et al., Rhom-2 expression does not always correlate with abnormalities on chromosome 11 at band p13 in T-cell acute lymphoblastic leukemia, Blood, 1992, 80: 3189–3197.

    PubMed  CAS  Google Scholar 

  13. Robb, L., Lyons, I., Li, R. et al., Absence of yolk sac hematopoiesis from mice with a targeted disruption of the scl gene, Proc. Natl. Acad. Sci. USA. 1995, 92: 7075–7079.

    Article  PubMed  CAS  Google Scholar 

  14. Shivdasani, R. A., Mayer, E. L., Orkin, S. H., Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL, Nature, 1995, 373: 432–434.

    Article  PubMed  CAS  Google Scholar 

  15. Aplan, P. D., Jones, C. A., Chervinsky, D. S. et al., An scl gene product lacking the transactivation domain induces bony abnormalities and cooperates with LMO1 to generate T-cell malignancies in transgenic mice, EMBO J, 1997, 16: 2408–2419.

    Article  PubMed  CAS  Google Scholar 

  16. Valge-Archer, V. E., Osada, H., Warren, A. J. et al., The LIM protein RBTN2 and the basic helix-loop-helix protein TAL1 are present in a complex in erythroid cells, Pro. Natl. Acad. Sci. USA, 1994, 91: 8617–8621.

    Article  CAS  Google Scholar 

  17. Wadman, I., Li, J., Bash, R. et al., Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia, EMBO J., 1994, 13: 4831–4839.

    PubMed  CAS  Google Scholar 

  18. Wadman, I. A., Osada, H., Grutz, G. G. et al., The LIM-only protein Lmo2 is a bridging molecule assembling an erythroid, DNA-binding complex which includes the TAL1, E47, GATA1 and Ldb1/NLI proteins, EMBO J., 1997, 16: 3145–3157.

    Article  PubMed  CAS  Google Scholar 

  19. Visvader, J. E., Mao, X. H., Fujiwara, Y. et al., The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation, Proc. Natl. Acad. Sci. USA, 1997, 94: 13707–13712.

    Article  PubMed  CAS  Google Scholar 

  20. Zhou, Y., Du, G. W., Wang, J. H. et al., The separation and cloning of human LDB1 cDNA, Chinese Science Bulletin, 1999, 44(8): 755–760.

    Google Scholar 

  21. Grutz, G. G., Bucher, K., Lavenir, I. et al., The oncogenic T cell LIM-protein Lmo2 forms part of a DNA-binding complex specifically in immature T cells, EMBO J., 1998, 17: 4594–4605.

    Article  PubMed  CAS  Google Scholar 

  22. Rabbitts, T. H., LMO T-cell translocation oncogenes typify genes activated by chromosomal translocations that alter transcription and developmental processes, Gene & Dev., 1998, 12: 2651–2657.

    Article  CAS  Google Scholar 

  23. Rabbitts, T. H., Bucher, K., Chung, G. et al., The effect of chromosomal translocations in acute leukemias: The LMO2 paradigm in transcription and development, Cancer Res., 1999, 39: 1794–1798.

    Google Scholar 

  24. Foroni, L., Boehm, T., White, L. et al., The rhombotin gene family encode related LIM-domain proteins whose differing expression suggests multiple roles on mouse development, J. Mol. Biol., 1992, 226: 747–761.

    Article  PubMed  CAS  Google Scholar 

  25. Bernard, O., Lecointe, N., Jonveaux, P. et al., Two site-specific deletions and t(1;14) translocation restricted to human T-cell acute leukemias disrupt the 5′part of the TAL1 gene, Oncogene, 1991, 6: 1477–1488.

    PubMed  CAS  Google Scholar 

  26. Cheng, J. T., Hsu, H. L., Hwang, L. Y. et al., Products of the TAL1 oncogene: basic helix-loop-helix proteins phosphorylated at serine residues, Oncogene, 1993, 8: 677–683.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Medical College, Nankai University, 300071, Tianjin, China

    Tianhui Zhu & Gang Qin

  2. Institute of Humangenetics, Duesseldorf University, 40225, Duesseldorf, Germany

    Brigitte Royer-Pokora

Authors
  1. Tianhui Zhu
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  2. Gang Qin
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  3. Brigitte Royer-Pokora
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Correspondence to Tianhui Zhu.

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Zhu, T., Qin, G. & Royer-Pokora, B. A novel post-transcriptional splicing form of the acute T cell leukemia proto-oncogeneLmo2 . Sci. China Ser. C.-Life Sci. 44, 561–569 (2001). https://doi.org/10.1007/BF02879349

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  • DOI: https://doi.org/10.1007/BF02879349

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