Identification and characterization of BCL-3-binding protein: implications for transcription and DNA repair or recombination.
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.
Department of Tumor Cell Biology, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
Nobumasa
N
Watanabe
Sumiko
S
Wachi
Takashi
T
Fujita
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D001402:B-Lymphocytes / Q000378:metabolism; D017122:Bacteriophage T4 / Q000378:metabolism; D001665:Binding Sites; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D004260:DNA Repair; D045643:DNA Repair Enzymes; D018076:DNA, Complementary / Q000378:metabolism; D050881:E1A-Associated p300 Protein; D005822:Genetic Vectors; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011116:Polynucleotide 5'-Hydroxyl-Kinase / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D020798:Two-Hybrid System Techniques
D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; C000631345:Bcl3 protein, mouse; D002352:Carrier Proteins; D018076:DNA, Complementary; C476254:N4BP2 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000255:Adenosine Triphosphate; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; D005982:Glutathione Transferase; D011116:Polynucleotide 5'-Hydroxyl-Kinase; D045643:DNA Repair Enzymes