Abstract
Background: Chromosomal aberrations of BCLIIA at 2p16.1 have been reported in a variety of B-cell malignancies and its deficiency in mice leads to a profound block in B-cell development. Results: Alternative pre-mRNA splicing of BCLIIA produces multiple isoforms sharing a common N-terminus. The most abundant isoform we have identified in human lymphoid samples is BCLIIA-XL, the longest transcript produced at this locus, and here we report the conservation of this major isoform and its functional characterization. We show that BCLIIA-XL is a DNA-sequence-specific transcriptional repressor that associates with itself and with other BCLIIA isoforms, as well as with the BCL6 proto-oncogene. Western blot data for BCLIIA-XL expression coupled with data previously published for BCL6 indicates that these genes are expressed abundantly in germinal-center-derived B cells but that expression is extinguished upon terminal differentiation to the plasma cell stage. Although BCLIIA-XL/BCL6 interaction can modulate BCL6 DNA binding in vitro, their heteromeric association does not alter the homomeric transcriptional properties of either on model reporter activity. BCLIIA-XL partitions into the nuclear matrix and colocalizes with BCL6 in nuclear paraspeckles. Conclusion: We propose that the conserved N-terminus of BCLIIA defines a superfamily of C2HC zinc-finger transcription factors involved in hematopoietic malignancies.
Original language | English (US) |
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Article number | 18 |
Journal | Molecular Cancer |
Volume | 5 |
DOIs | |
State | Published - May 16 2006 |
ASJC Scopus subject areas
- Molecular Medicine
- Oncology
- Cancer Research