Constitutive expression of Bc1-3 in thymocytes increases the DNA binding of NF-kappaB1 (p50) homodimers in vivo.
Previous studies have indicated that Bcl-3 interacts through its ankyrin repeats with the transcriptional factors NF-kappaB1 (p50) and NF-kappaB2 (p52), affecting their biological activities. To further investigate the role of Bcl-3 in vivo and its association with the NF-kappaB proteins, we have generated transgenic mice constitutively expressing Bcl-3 in thymocytes. The results indicate that Bcl-3 is associated with endogenous p50 and p52 in nuclear extracts from transgenic animals. Remarkably, constitutive expression of Bcl-3 in these cells augments the DNA binding activity of p52 homodimers. This effect could be reproduced in vitro and is blocked by anti-Bcl-3 antibodies. We have also shown that Bcl-3 is phosphorylated in thymocytes and that its dephosphorylation greatly decreases the effect on p50 homodimers.
Caamaño
J H
JH
Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
Perez
P
P
Lira
S A
SA
Bravo
R
R
D000818:Animals; D017487:Ankyrins / Q000378:metabolism; D000081242:B-Cell Lymphoma 3 Protein; D015153:Blotting, Western; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D005434:Flow Cytometry; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors; D015533:Transcriptional Activation
D017487:Ankyrins; D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D004247:DNA