P105 AND P98 PRECURSOR PROTEINS PLAY AN ACTIVE-ROLE IN NF-KAPPA-B-MEDIATED SIGNAL TRANSDUCTION
P105 AND P98 PRECURSOR PROTEINS PLAY AN ACTIVE-ROLE IN NF-KAPPA-B-MEDIATED SIGNAL TRANSDUCTION
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DOI：
10.1101/gad.7.4.705
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发表时间：
1993-04-01
影响因子：
10.5
通讯作者：
KARIN, M
中科院分区：
文献类型：
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作者：
MERCURIO, F;DIDONATO, JA;KARIN, M
Rel/NF-kappaB转录因子家族由两个不同的亚群组成，一种是经过蛋白水解加工的蛋白质，在其羧基末端含有SWI6/锚蛋白重复序列（p105, p98），另一种是不需要加工的重复序列（p65, c-Rel， RelB和Dorsal）。我们证明p105和p98前体与IkappaB蛋白具有相同的功能特性，后者也含有SWI6/锚蛋白重复序列。发现p105和p98与其他Rel/NF-kappaB家族成员（包括p65和c-Rel）形成稳定的复合物。与前体的结合足以使p65或c-Rel在细胞质中保留，否则它们都是核的。这些复合物经过刺激反应加工产生活性p50/c-Rel和p55/c-Rel复合物。这些观察结果提示了导致NF-kappaB诱导的第二种途径，其中前体的加工而不是IkappaB的磷酸化起主要作用。
The Rel/NF-kappaB family of transcription factors is composed of two distinct subgroups, proteins that undergo proteolytic processing and contain SWI6/ankyrin repeats in their carboxyl termini (p105, p98), and those without such repeats that do not require processing (p65, c-Rel, RelB, and Dorsal). We demonstrate that the p105 and p98 precursors share functional properties with the IkappaB proteins, which also contain SWI6/ankyrin repeats. Both p105 and p98 were found to form stable complexes with other Rel/NF-kappaB family members, including p65 and c-Rel. Association with the precursors is sufficient for cytoplasmic retention of either p65 or c-Rel, both of which are otherwise nuclear. These complexes undergo stimulus-responsive processing to produce active p50/c-Rel and p55/c-Rel complexes. These observations suggest a second pathway leading to NF-kappaB induction, in which processing of the precursors rather than phosphorylation of IkappaB plays a major role.