title: The BAL-binding protein BBAP and related Deltex family members exhibit ubiquitin-protein isopeptide ligase activity.
abstract: Members of the DTX (Deltex) family act as Notch signaling modifiers and may also regulate transcription through interactions with specific transcription factors. DTX proteins have a basic N terminus; a central proline-rich region; and a C-terminal RING finger domain, a motif often found in ubiquitin-protein isopeptide ligases (E3). Recently, we identified and characterized a unique diffuse large B-cell lymphoma risk-related gene named BAL (B aggressive lymphoma). Using a yeast two-hybrid screen for BAL-binding partners, we have now identified a novel protein termed BBAP (B-lymphoma- and BAL-associated protein). Although BBAP has a unique N terminus, the C-terminal region is highly homologous to that of DTX family members. Herein, we report that BBAP and the human family of DTX proteins (DTX1, DTX2, and DTX3) function as E3 ligases based on their capacity for self-ubiquitination. DTX family members homodimerize and heterodimerize in vivo, suggesting that physical interactions between various DTX family members modify E3 activity and/or substrate availability. Consistent with this idea, BBAP and DTX1 associate via their unique N termini, resulting in enhanced self-ubiquitination.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Takeyama
authors.forename: Ricardo C T
authors.initials: RC
authors.lastname: Aguiar
authors.forename: Liqun
authors.initials: L
authors.lastname: Gu
authors.forename: Chunyan
authors.initials: C
authors.lastname: He
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Kutok
authors.forename: Jon C
authors.initials: JC
authors.lastname: Aster
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Shipp
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins; D002460:Cell Line; D019070:Cell Lineage; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D019281:Dimerization; D004331:Drosophila melanogaster; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008025:Ligases / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
chemical_list: D002352:Carrier Proteins; D011506:Proteins; D011994:Recombinant Proteins; D025801:Ubiquitin; C409218:deltex protein, vertebrate; C475669:DTX3L protein, human; D044767:Ubiquitin-Protein Ligases; D005982:Glutathione Transferase; D008025:Ligases