B-aggressive lymphoma family proteins have unique domains that modulate transcription and exhibit poly(ADP-ribose) polymerase activity

Ricardo C.T. Aguiar, Kunihiko Takeyama, Chunyan He, Katherine Kreinbrink, Margaret A. Shipp

    Research output: Contribution to journalArticle

    99 Scopus citations

    Abstract

    BAL1 (B-aggressive lymphoma 1) was originally identified as a risk-related gene in diffuse large B-cell lymphoma. BAL1 encodes a nuclear protein with N-terminal macro domains and a putative C-terminal poly(ADP-ribose) polymerase (PARP) active site. Macro domains are sequences homologous to the non-histone region of histone macroH2A. Several lines of evidence suggest that these domains may modulate transcription, including a high concentration of histone macroH2A in the inactive X chromosome, direct interference with transcription factor binding in a positioned nucleosome, and structural similarity to DNA binding domains. Poly(ADP-ribosyl)ation is a critical post-translational modification that regulates chromatin configuration and transcription. In this report we describe two additional BAL family members, BAL2 and BAL3, with N-terminal macro domains and putative C-terminal PARP active sites and assess the function of these specific regions in BAL family members. Herein, we demonstrate that BAL macro domains repress transcription when tethered to a promoter. In addition, we show that BAL2 and BAL3, but not BAL1, exhibit PARP activity. In agreement with these data, BAL1 lacks several critical donor and acceptor residues that are conserved in the BAL2 and -3 PARP active sites. Of interest, BAL family members with inactive or functional PARP domains differed in their ability to repress transcription. BAL family members are the only described proteins with both PARP and macro domains, underscoring the potential functional significance of this unique combination.

    Original languageEnglish (US)
    Pages (from-to)33756-33765
    Number of pages10
    JournalJournal of Biological Chemistry
    Volume280
    Issue number40
    DOIs
    StatePublished - Oct 7 2005

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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