Identification and characterization of BCL-3-binding protein: implications for transcription and DNA repair or recombination

J Biol Chem. 2003 Jul 11;278(28):26102-10. doi: 10.1074/jbc.M303518200. Epub 2003 May 2.

Abstract

A putative oncogene bcl-3 was originally identified and cloned at the breakpoint in the recurring chromosome translocation t(14;19) found in some cases of B cell chronic lymphocytic leukemia. Studies of bcl-3-deficient mice demonstrated a critical role for bcl-3 in the development of a normal immune response and the formation of germinal centers in secondary lymphoid organs. However, the molecular mechanism that underlies B cell leukemogenesis and the knockout mouse phenotype remains unclear. Here we have identified and characterized BCL-3-binding protein (B3BP) as a protein interacting specifically with the bcl-3 gene product (BCL-3) by a yeast two-hybrid screen. We found that B3BP associates with not only BCL-3 but also p300/CBP histone acetyltransferases. The N-terminal region of B3BP that contains the ATP-binding site is important for the interaction with BCL-3 and p300/CBP. Homology searches indicate that the ATP-binding region of B3BP, which contains a typical Walker-type ATP-binding P-loop, most resembles that of 2',3'-cyclic nucleotide 3'-phosphodiesterase of mammals and polynucleotide kinase of T4 bacteriophage. In fact B3BP shows intrinsic ATP binding and hydrolyzing activity. Furthermore, we demonstrated that B3BP is a 5'-polynucleotide kinase. We also found a small MutS-related domain, which is thought to be involved in the DNA repair or recombination reaction, in the C-terminal region of B3BP, and it shows nicking endonuclease activity. These observations might help to gain new insights into the function of BCL-3 and p300/CBP, especially the coupling of transcription with repair or recombination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Animals
  • B-Cell Lymphoma 3 Protein
  • B-Lymphocytes / metabolism
  • Bacteriophage T4 / metabolism
  • Binding Sites
  • Blotting, Western
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Cell Line
  • DNA Repair
  • DNA Repair Enzymes
  • DNA, Complementary / metabolism
  • E1A-Associated p300 Protein
  • Genetic Vectors
  • Glutathione Transferase / metabolism
  • Humans
  • Hydrolysis
  • Mice
  • Mice, Knockout
  • Models, Genetic
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism*
  • Plasmids / metabolism
  • Polynucleotide 5'-Hydroxyl-Kinase / metabolism
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / metabolism*
  • Recombinant Proteins / metabolism
  • Recombination, Genetic*
  • Sequence Homology, Amino Acid
  • Time Factors
  • Trans-Activators / metabolism*
  • Transcription Factors
  • Transcription, Genetic*
  • Transfection
  • Two-Hybrid System Techniques

Substances

  • B-Cell Lymphoma 3 Protein
  • BCL3 protein, human
  • Bcl3 protein, mouse
  • Carrier Proteins
  • DNA, Complementary
  • N4BP2 protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • Trans-Activators
  • Transcription Factors
  • Adenosine Triphosphate
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse
  • Glutathione Transferase
  • Polynucleotide 5'-Hydroxyl-Kinase
  • DNA Repair Enzymes