GENERATION OF P50 SUBUNIT OF NF-KAPPA-B BY PROCESSING OF P105 THROUGH AN ATP-DEPENDENT PATHWAY

GENERATION OF P50 SUBUNIT OF NF-KAPPA-B BY PROCESSING OF P105 THROUGH AN ATP-DEPENDENT PATHWAY
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DOI:
10.1038/354395a0
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发表时间:
1991-12-05
期刊:
影响因子:
64.8
通讯作者:
MANIATIS, T
MANIATIS, T
中科院分区:
综合性期刊1区
文献类型:
--
作者:
FAN, CM;MANIATIS, T

文献摘要

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转录因子NF-κ-B是由rel基因家族的不同成员(p50和p65)1-7编码的两种蛋白质组成的异源二聚体。p50亚基在DNA结合蛋白中是不寻常的,因为其功能形式在相对分子质量为105,000的开放阅读框架中编码(p105;参考文献4)。该开放阅读框的N-末端区域编码p50,而剩余的C-末端包含锚蛋白重复。尽管p50与DNA结合,但在体外翻译的全长p105不结合4,5。p50在体内产生的机制和p105 C-末端区域的命运尚未确定。在这里,我们表明,功能性p50是由ATP依赖的p105蛋白水解。此外,我们发现,C-末端的一半的p 105是不需要在体内加工,并迅速降解加工。我们认为p105的C-末端区域参与了p50/p65异源二聚体和抑制剂I-kappa-B之间复合物的胞质组装。
THE transcription factor NF-kappa-B is a heterodimer consisting of two proteins encoded by different members of the rel gene family (p50 and p65) 1-7. The p50 subunit is unusual among DNA-binding proteins in that its functional form is encoded in an open reading frame of relative molecular mass 105,000 (p105; ref. 4). The N-terminal region of this open reading frame encodes p50, whereas the remaining C terminus contains ankyrin repeats. Although p50 binds to DNA, full-length p105 translated in vitro does not 4,5. The mechanism by which p50 is generated in vivo, and the fate of the C-terminal region of p105 have not been established. Here we show that functional p50 is produced by ATP-dependent proteolysis of p105. Moreover, we find that the C-terminal half of p 105 is not required for processing in vivo, and is rapidly degraded on processing. We propose that the C-terminal region of p105 is involved in the cytoplasmic assembly of the complex between the p50/p65 heterodimer and the inhibitor I-kappa-B.