THE PROTOONCOGENE BCL-3 ENCODES AN I-KAPPA-B PROTEIN
THE PROTOONCOGENE BCL-3 ENCODES AN I-KAPPA-B PROTEIN
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DOI：
10.1101/gad.6.12a.2352
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发表时间：
1992-12-01
影响因子：
10.5
通讯作者：
VERMA, IM
中科院分区：
文献类型：
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作者：
KERR, LD;DUCKETT, CS;VERMA, IM
bcl-3 基因产物在具有 t(14;19) 易位的慢性淋巴细胞白血病 (CLL) 患者中过度表达，是 IkappaB 家族的成员。 bcl-3 蛋白能够抑制真正的 NF-kappaB 异二聚体 p50-p65 和 p49-p65 以及 p50 和 p49 同二聚体的 DNA 结合和反式激活。 bcl-3 蛋白不会抑制 Rel 蛋白的 DNA 结合活性或其反式激活与 kappaB 位点相连的基因的能力。之前被鉴定为 IkappaB 家族成员的人类 37-kD 蛋白 (IkappaBalpha) 也无法抑制 Rel 蛋白的 DNA 结合活性。然而，与 bcl-3 不同，37 kD (IkappaBalpha) 蛋白对 p50 或 p49 同二聚体的 DNA 结合活性没有影响。人 bcl-3 和人 37-kD (IkappaBalpha) 蛋白的二维磷酸胰蛋白酶肽图显示，37-kD (IkappaBalpha) 蛋白的磷酸肽嵌套在 bcl-3 蛋白内。此外，bcl-3 抗血清可免疫沉淀体外放射性标记的 37-kD (IkappaBalpha) 蛋白。在用 PMA 刺激并用 bcl-3 抗血清免疫沉淀的 HeLa 细胞中可以鉴定 56 和 38 kD 的蛋白质。体外合成的 bcl-3 蛋白以及来自 HeLa 细胞的 p56 和 p38 的胰蛋白酶肽图的比较表明，它们在结构上都是相关的。去除 bcl-3 蛋白的氨基末端序列会产生一种抑制 p50-p65 异二聚体 DNA 结合的蛋白，但与 37-kD (IkappaBalpha) 蛋白一样，不再能够抑制 p50 和 p49 同二聚体与 kappaB DNA 的结合。我们认为 bcl-3 和 37-kD (IkappaBalpha) 蛋白是相关的并且是 IkappaB 家族的成员。
The bcl-3 gene product, overexpressed in chronic lymphocytic leukemia (CLL) patients with the translocation t(14;19), is a member of the IkappaB family. The bcl-3 protein is able to inhibit the DNA binding and trans-activation of authentic NF-kappaB heterodimers p50-p65 and p49-p65, as well as p50 and p49 homodimers. The bcl-3 protein does not inhibit either the DNA-binding activity of the Rel protein or its ability to trans-activate genes linked to the kappaB site. A human 37-kD protein (IkappaBalpha), identified previously as a member of the IkappaB family, is also unable to inhibit DNA-binding activity of the Rel protein. However, unlike bcl-3, the 37-kD (IkappaBalpha) protein has no effect on the DNA-binding activity of p50 or p49 homodimers. Two dimensional phosphotryptic peptide maps of the human bcl-3 and the human 37-kD (IkappaBalpha) proteins reveal that the phosphopeptides from the 37-kD (IkappaBalpha) protein are nested within the bcl-3 protein. Furthermore, bcl-3 antisera immunoprecipitates an in vitro-radiolabeled 37-kD (IkappaBalpha) protein. Proteins of 56 and 38 kD can be identified in HeLa cells stimulated with PMA and immunoprecipitated with bcl-3 antisera. Comparison of tryptic peptide maps of the bcl-3 protein synthesized in vitro, and p56 and p38 from HeLa cells, shows that they are all structurally related. Removal of the amino-terminal sequences of the bcl-3 protein generates a protein that inhibits the DNA binding of the p50-p65 heterodimer but, like the 37-kD (IkappaBalpha) protein, is no longer able to inhibit the binding of the p50 and p49 homodimers with kappaB DNA. We propose that the bcl-3 and 37-kD (IkappaBalpha) proteins are related and are members of the IkappaB family.