Expression and transcriptional regulation of functionally distinct Bmf isoforms in B-chronic lymphocytic leukemia cells

Leukemia. 2004 Jan;18(1):41-7. doi: 10.1038/sj.leu.2403183.

Abstract

Bmf is a BH3-only Bcl-2 family member that is normally sequestered to myosin V motors by binding to the dynein light chain 2 (DLC2). Certain damage signals release Bmf, which then binds prosurvival Bcl-2 proteins and triggers apoptosis. Here, two novel isoforms of human Bmf, Bmf-II and Bmf-III, were identified and cloned from cDNA derived from B-chronic lymphocytic leukemia (B-CLL) cells. Bmf-II and Bmf-III were characterized as two splice variants, lacking the BH3 domain but retaining the DLC2 binding domain. Bmf (here called Bmf-I) expression in HeLa cells induced apoptosis and reduced colony formation in contrast to Bmf-II and Bmf-III, which had no effect on apoptosis and instead increased colony formation. While bmf-I mRNA was expressed in many cell types, expression was higher in B lymphoid cells and bmf-II and bmf-III were mainly detected in B-CLL and normal B cells. bmf-I mRNA was upregulated in normal and leukemic B cells, while bmf-III mRNA was downregulated only in B-CLL cells by serum deprivation. We show that Bmf is regulated by transcriptional activation and alternative splicing and conclude that the relative levels of Bmf isoforms may have a role in regulating growth and survival in B cells and leukemic B-CLL cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Alternative Splicing
  • Apoptosis*
  • B-Lymphocytes / metabolism
  • Base Sequence
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Culture Media, Serum-Free
  • DNA, Complementary / genetics
  • DNA, Complementary / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Molecular Sequence Data
  • Protein Isoforms
  • RNA, Messenger / metabolism
  • Sequence Homology, Nucleic Acid
  • Transcription, Genetic
  • Transfection

Substances

  • Adaptor Proteins, Signal Transducing
  • BMF protein, human
  • Carrier Proteins
  • Culture Media, Serum-Free
  • DNA, Complementary
  • Protein Isoforms
  • RNA, Messenger