Caamaño J H, Perez P, Lira S A, Bravo R
Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
Mol Cell Biol. 1996 Apr;16(4):1342-8. doi: 10.1128/MCB.16.4.1342.
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.
先前的研究表明,Bcl-3通过其锚蛋白重复序列与转录因子NF-κB1(p50)和NF-κB2(p52)相互作用,影响它们的生物学活性。为了进一步研究Bcl-3在体内的作用及其与NF-κB蛋白的关联,我们构建了在胸腺细胞中组成性表达Bcl-3的转基因小鼠。结果表明,在转基因动物的核提取物中,Bcl-3与内源性p50和p52相关联。值得注意的是,这些细胞中Bcl-3的组成性表达增强了p52同二聚体的DNA结合活性。这种效应在体外可以重现,并且被抗Bcl-3抗体阻断。我们还表明,Bcl-3在胸腺细胞中被磷酸化,其去磷酸化大大降低了对p50同二聚体的影响。