Functional studies of BCLIIA: Characterization of the conserved BCLIIA-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells

Hui Liu, Gregory C. Ippolito, Jason K. Wall, Teresa Niu, Loren Probst, Baeck Seung Lee, Karen Pulford, Alison H. Banham, Luke Stockwin, Arthur L. Shaffer, Louis M. Staudt, Chhaya Das, Martin J.S. Dyer, Philip W. Tucker

Research output: Contribution to journalArticle

50 Scopus citations

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 languageEnglish (US)
Article number18
JournalMolecular Cancer
Volume5
DOIs
StatePublished - May 16 2006

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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