THE BCL-3 PROTOONCOGENE ENCODES A NUCLEAR I-KAPPA-B-LIKE MOLECULE THAT PREFERENTIALLY INTERACTS WITH NF-KAPPA-B P50 AND P52 IN A PHOSPHORYLATION-DEPENDENT MANNER
THE BCL-3 PROTOONCOGENE ENCODES A NUCLEAR I-KAPPA-B-LIKE MOLECULE THAT PREFERENTIALLY INTERACTS WITH NF-KAPPA-B P50 AND P52 IN A PHOSPHORYLATION-DEPENDENT MANNER
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DOI：
10.1128/mcb.13.6.3557
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发表时间：
1993-06-01
影响因子：
5.3
通讯作者：
BALTIMORE, D
中科院分区：
文献类型：
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作者：
NOLAN, GP;FUJITA, T;BALTIMORE, D
推定的原癌基因bcl-3的产物是一种IkappaB样分子，其具有对rel家族转录调节因子的一个子集具有特异性的新型结合特性。在体外，Bcl-3蛋白特异性抑制同源二聚体NF-κ B p50亚基和密切相关的同源物p52（以前的p49）与免疫球蛋白κ NF-κ B DNA基序的DNA结合。Bcl-3可以催化这些蛋白质从DNA中去除。在显著抑制同二聚体p50的DNA结合的浓度下，Bcl-3不抑制重组异二聚体NF-κ B（p50：p65）、p65的DNA结合同二聚体形式或c-Rel的同二聚体的结合。磷酸酶处理Bcl-3部分灭活其抑制特性，暗示了磷酸化在Bcl-3活性调节中的作用。Bcl-3和p50一样，定位于细胞核。在Bcl-3和p50共转导的细胞中，两种分子都可以在同一细胞的细胞核中找到。有趣的是，Bcl-3与缺失其核定位信号的p50突变体的共表达导致Bcl-3重新定位于细胞质，表明蛋白质在细胞中相互作用。这些特性将Bcl-3与经典定义的IkappaB形成对比，IkappaB通过与p65亚基的特异性相互作用在细胞质中维持异源二聚体NF-κ B p50：p65。Bcl-3似乎是一种核IkappaB相关分子，调节同源二聚体核p50及其同源物p52的活性。
The product of the putative proto-oncogene bcl-3 is an IkappaB-like molecule with novel binding properties specific for a subset of the rel family of transcriptional regulators. In vitro, Bcl-3 protein specifically inhibited the DNA binding of both the homodimeric NF-kappaB p50 subunit and a closely related homolog, p52 (previously p49), to immunoglobulin kappa NF-kappaB DNA motifs. Bcl-3 could catalyze the removal of these proteins from DNA. At concentrations that significantly inhibited DNA binding by homodimeric p50, Bcl-3 did not inhibit binding of reconstituted heterodimeric NF-kappaB (p50:p65), a DNA-binding homodimeric form of p65, or homodimers of c-Rel. Phosphatase treatment of Bcl-3 partially inactivated its inhibitory properties, implicating a role for phosphorylation in the regulation of Bcl-3 activity. Bcl-3, like p50, localizes to the cell nucleus. In cells cotransduced with Bcl-3 and p50, both molecules could be found in the nucleus of the same cells. Interestingly, coexpression of Bcl-3 with a p50 mutant deleted for its nuclear-localizing signal resulted in the relocalization of Bcl-3 to the cytoplasm, showing that the proteins interact in the cell. These properties contrast Bcl-3 to classically defined IkappaB, which maintains heterodimeric NF-kappaB p50:p65 in the cytoplasm through specific interactions with the p65 subunit. Bcl-3 appears to be a nuclear, IkappaB-related molecule that regulates the activity of homodimeric nuclear p50 and its homolog p52.