Modification by Single Ubiquitin Moieties Rather Than Polyubiquitination Is Sufficient for Proteasomal Processing of the p105 NF-κB Precursor
Modification by Single Ubiquitin Moieties Rather Than Polyubiquitination Is Sufficient for Proteasomal Processing of the p105 NF-κB Precursor
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DOI：
10.1016/j.molcel.2009.01.023
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发表时间：
2009-02-27
期刊：
影响因子：
16
通讯作者：
Ciechanover, Aaron
中科院分区：
文献类型：
--
作者：
Kravtsova-Ivantsiv, Yelena;Cohen, Shai;Ciechanover, Aaron
NF-κ B的活化通过许多泛素和蛋白酶体介导的步骤进行调节;重要的步骤是将前体p105加工成p50活性亚基。其中涉及的机制在很大程度上是未知的，因为这是一个例外的情况下，泛素系统不完全破坏其底物。在这里，我们表明，蛋白酶体处理p105需要泛素，但不产生聚泛素链。在体外，泛素不能介导加工。在表达不可聚合的泛素的酵母中，加工正常进行，而依赖于多聚泛素化的底物的降解被抑制。在哺乳动物细胞中也得到了类似的结果。有趣的是，加工需要多次单泛素化，因为p105中赖氨酸的逐渐消除伴随着p50生成的逐渐抑制。最后，蛋白酶体识别多重单泛素化的p105。这些发现表明，蛋白水解信号可以由单个泛素的簇组成，而不一定是一条链。
Activation of NF-kappa B is regulated via numerous ubiquitin- and proteasome-mediated steps; an important one is processing of the precursor p105 to the p50 active subunit. The mechanisms involved are largely unknown, because this is an exceptional case where the ubiquitin system does not destroy its substrate completely. Here, we demonstrate that proteasomal processing of p105 requires ubiquitin but not generation of polyubiquitin chains. In vitro, ubiquitin species that cannot polymerize mediate processing. In yeasts that express nonpolymerizable ubiquitins, processing proceeds normally, whereas degradation of substrates that are dependent on polyubiquitination is inhibited. Similar results were obtained in mammalian cells. Interestingly, processing requires multiple monoubiquitinations, because progressive elimination of lysines in p105 is accompanied by gradual inhibition of p50 generation. Finally, the proteasome recognizes the multiply monoubiquitinated p105. These findings suggest that a proteolytic signal can be composed of a cluster of single ubiquitins, not necessarily a chain.