Mammalian Genome

, Volume 12, Issue 2, pp 163–168

Gene structure, alternative splicing, and chromosomal localization of pro-apoptotic Bcl-2 relative Bim

Authors

  • Philippe  Bouillet
    • The Walter and Eliza Hall Institute of Medical Research, P.O. The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia
  • Li Chen  Zhang
    • The Walter and Eliza Hall Institute of Medical Research, P.O. The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia
  • David C.S.  Huang
    • The Walter and Eliza Hall Institute of Medical Research, P.O. The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia
  • Graham C.  Webb
    • Department of Obstetrics & Gynaecology, The Queen Elizabeth Hospital, The University of Adelaide, Glen Osmond, South Australia, 5064, Australia
  • Cynthia D.K.  Bottema
    • Department of Animal Science, Waite Campus, The University of Adelaide, Glen Osmond, South Australia, 5064, Australia
  • Paul  Shore
    • School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK
  • Helen J.  Eyre
    • Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, Adelaide, South Australia, 5006, Australia
  • Grant R.  Sutherland
    • Centre for Medical Genetics, Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, Adelaide, South Australia, 5006, Australia
  • Jerry M.  Adams
    • The Walter and Eliza Hall Institute of Medical Research, P.O. The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia

DOI: 10.1007/s003350010242

Cite this article as:
Bouillet, P., Zhang, L., Huang, D. et al. (2001) 12: 163. doi:10.1007/s003350010242

Abstract.

Bim is a proapoptotic protein of the Bcl-2 family that shares only the short BH3 domain with other members. It has three isoforms, apparently produced by alternative splicing. The demonstration that Bim is essential for certain apoptotic responses and to prevent overproduction of hematopoietic cells suggests that it may be a tumor suppressor. We have, therefore, investigated the organization of the mouse Bim gene, delineating its promoter and splicing, and positioned the gene on both mouse and human chromosomes. Bim has six exons, but the third is a facultative intron that is spliced out in the mRNAs for the smaller isoforms (BimL and BimS), but not that encoding the largest isoform (BimEL). The 0.8-kb region 5′ to exon 1, which contains a TATA-less promoter and binding sites for several transcription factors, can drive expression of a reporter gene. Mouse Bim localizes to the distal third of Chromosome (Chr) 2, near the F-G boundary, and its human counterpart to Chr 2q12 or q13. Deletions of these bands have been reported in ten tumors (eight hematopoietic), reinforcing the possibility that Bim is a tumor suppressor. These findings should help to clarify the regulation of Bim expression and to assess whether mutations involving Bim contribute to neoplastic and other diseases.

Copyright information

© Springer-Verlag New York Inc. 2001