I kappa B epsilon, a novel member of the I kappa B family, controls RelA and cRel NF-kappa B activity
I kappa B epsilon, a novel member of the I kappa B family, controls RelA and cRel NF-kappa B activity
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DOI：
10.1093/emboj/16.6.1413
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发表时间：
1997-03-17
期刊：
影响因子：
11.4
通讯作者：
Israel, A
中科院分区：
文献类型：
--
作者：
Whiteside, ST;Epinat, JC;Israel, A
我们使用酵母双杂交筛选能够与转录因子 NF-kappa B 的 p52 亚基相互作用的蛋白质，分离出编码新型 I kappa B 家族成员的人类 cDNA。该蛋白质存在于许多细胞类型中，其表达在 NF-kappa B 激活后和骨髓生成过程中上调。与其作为 I kappa B 分子的作用一致，I kappa B-epsilon 能够通过 rel 蛋白的细胞质保留来抑制 NF-kappa B 定向的反式激活。 I kappa B-epsilon 翻译从内部 ATG 密码子开始，产生 45 kDa 的蛋白质，该蛋白质在静息细胞中以多种磷酸化亚型存在。与其他抑制剂不同，它几乎只存在于含有 RelA 和/或 cRel 的复合物中。激活后，I kappa B-epsilon 蛋白通过蛋白酶体依赖性机制以缓慢的动力学降解。与 I kappa B-alpha 和 I kappa B-beta 类似，I kappa B-epsilon 包含多个锚蛋白重复序列和两个保守丝氨酸，它们是信号诱导的分子降解所必需的。位于丝氨酸 N 端的独特赖氨酸残基似乎并不是降解所必需的，与 I kappa B-alpha 和 I kappa B-beta 不同，I kappa B-epsilon 不包含 C 端 PEST 样序列。因此，I kappa B-epsilon 似乎可以调节由 RelA/cRel NF-kappa B 复合物调节的基因子集的晚期、瞬时激活，这与其他 I kappa B 蛋白调节的基因不同。
We have isolated a human cDNA which encodes a novel I kappa B family member using a yeast two-hybrid screen for proteins able to interact with the p52 subunit of the transcription factor NF-kappa B. The protein is found in many cell types and its expression is up-regulated following NF-kappa B activation and during myelopoiesis. Consistent with its proposed role as an I kappa B molecule, I kappa B-epsilon is able to inhibit NF-kappa B-directed transactivation via cytoplasmic retention of rel proteins. I kappa B-epsilon translation initiates from an internal ATG codon to give rise to a protein of 45 kDa, which exists as multiple phosphorylated isoforms in resting cells. Unlike the other inhibitors, it is found almost exclusively in complexes containing RelA and/or cRel. Upon activation, I kappa B-epsilon protein is degraded with slow kinetics by a proteasome-dependent mechanism. Similarly to I kappa B-alpha and I kappa B-beta, I kappa B-epsilon contains multiple ankyrin repeats and two conserved serines which are necessary for signal-induced degradation of the molecule. A unique lysine residue located N-terminal of the serines appears to be not strictly required for degradation, Unlike I kappa B-alpha and I kappa B-beta, I kappa B-epsilon does not contain a C-terminal PEST-like sequence. I kappa B-epsilon would, therefore, appear to regulate a late, transient activation of a subset of genes, regulated by RelA/cRel NF-kappa B complexes, distinct from those regulated by other I kappa B proteins.