Regulation of NFKB1 proteins by the candidate oncoprotein BCL-3: generation of NF-kappaB homodimers from the cytoplasmic pool of p50-p105 and nuclear translocation.
The candidate oncoprotein BCL-3 has been shown to function as a transcriptional co-activator for homodimers of NF-kappaB p50 and p50B. We expressed BCL-3 ectopically in pro-B cell lines and found that these cells exhibited a dramatic increase in nuclear kappaB motif binding activity of p50 homodimers containing BCL-3 in the complex. Co-transfection and in vitro reconstitution experiments revealed that the complex of p50 with its precursor p105 (p50-p105), which was shown to accumulate in the cytoplasm of the pro-B cell lines, is required for induction of DNA binding of p50 homodimers by BCL-3. However, we could see no in vivo or in vitro evidence of a BCL-3-induced increase in proteolytic processing. Instead, BCL-3-mediated reorganization of NFKB1 subunits was demonstrated in vitro. Immunofluorescence staining clearly demonstrated that the transition from cytoplasmic p50-p105 to nuclear p50 homodimers was induced by BCL-3 expression. Thus BCL-3 has versatile functions: cytoplasmic activation of p50 homodimers, their nuclear translocation and, as previously shown, modulation of the transcriptional machinery in the nucleus.
Watanabe
N
N
Department of Tumor Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo, Japan.
Iwamura
T
T
Shinoda
T
T
Fujita
T
T
D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001692:Biological Transport; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D010450:Endopeptidases / Q000378:metabolism; D015870:Gene Expression; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D011498:Protein Precursors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D014157:Transcription Factors
D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011498:Protein Precursors; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D004247:DNA; D010450:Endopeptidases