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Runt domains take the lead in hematopoiesis and osteogenesis

Abstract

It has been nearly a decade since AML1 was first identified as the DNA-binding protein PEBP2αB/CBFA2 in mice. Molecular, genetic and biochemical studies have converged to reveal new information about how this unique family of transcription factors functions, and the linkage between developmental processes and human disease.

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Figure 1: Three-dimensional structure of the Runt domain and location of mutations causing deficiencies in DNA binding associated with AML, FPD and CCD.

References

  1. Look, A.T. Oncogenic transcription factors in the human acute leukemias. Science 278, 1059–1064 (1997).

    Article  CAS  PubMed  Google Scholar 

  2. Song, W.J. et al. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nature Genet. 23, 166–174 (1999).

    Article  CAS  PubMed  Google Scholar 

  3. Osato, M. et al. Biallelic and heterozygous point mutations in the runt domain of the AML1/PEBP2αB gene associated with myeloblastic leukemias. Blood 93, 1817–1824. (1999).

    CAS  PubMed  Google Scholar 

  4. Rodan, G.A. & Harada, S-I. The missing bone. Cell 89, 6777–680 (1997).

    Article  Google Scholar 

  5. Lee, B. et al. Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia. Nature Genet. 16, 307–310 (1997).

    Article  CAS  PubMed  Google Scholar 

  6. Mundlos, S. et al. Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell 89, 773–779 (1997).

    Article  CAS  PubMed  Google Scholar 

  7. Zhang, Y-W. et al. PEBP2αA/CBFA1 mutations in Japanese cleidocranial dysplasia patients. Gene (in the press).

  8. Nagata, T. et al. Immunoglobulin motif DNA recognition and heterodimerization of the PEBP2/CBF Runt domain. Nature Struct. Biol. 6, 615–619 (1999).

    Article  CAS  PubMed  Google Scholar 

  9. Goger, M. et al. Molecular insights into PEBP2/CBFβ-SMMHC associated acute leukemia revealed from the structure of PEBP2/CBFβ Nature Struct. Biol. 6, 620–623 (1999).

  10. Huang, X. et al. Solution structure of CBFβ and a map of the CBFα binding site. Nature Struct. Biol. 6, 624–627 (1999).

    Article  CAS  PubMed  Google Scholar 

  11. Berardi, M.J. et al. The Ig fold of the core binding factor α Runt domain is a member of a family of structurally and functionally related Ig-fold DNA-binding domains. Structure 7, 1247–137 (1999).

    Article  CAS  PubMed  Google Scholar 

  12. Wang, Q. et al. Disruption of the CBFA2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proc. Natl. Acad. Sci. USA 93, 3444–3449 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Okuda, T. et al. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell 84, 321–330 (1996).

    Article  CAS  PubMed  Google Scholar 

  14. Hanai, J. et al. Interaction and functional cooperation of PEBP2/CBF with Smads. J. Biol. Chem. 274, 31577–31582 (1999).

    Article  CAS  PubMed  Google Scholar 

  15. Knudson, A.G. Jr. Mutation and cancer: statistical study of retinoblastoma. Proc. Natl. Acad. Sci. USA 68, 820–823 (1971).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Fero, M.L. et al. The murine gene p27Kip1 is haplo-insufficient for tumour suppression. Nature 396, 177–180 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Werner, M., Shigesada, K. & Ito, Y. Runt domains take the lead in hematopoiesis and osteogenesis. Nat Med 5, 1356–1357 (1999). https://doi.org/10.1038/70920

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