Department of Immunology and Genetics and Biotechnology, Hebrew University-Hadassah Medical School, Institute of Medical Research Israel-Canada, Jerusalem, 91120, Israel.
Cold Spring Harb Perspect Biol. 2010 Feb;2(2):a000166. doi: 10.1101/cshperspect.a000166.
The key step in NF-kappaB activation is the release of the NF-kappaB dimers from their inhibitory proteins, achieved via proteolysis of the IkappaBs. This irreversible signaling step constitutes a commitment to transcriptional activation. The signal is eventually terminated through nuclear expulsion of NF-kappaB, the outcome of a negative feedback loop based on IkappaBalpha transcription, synthesis, and IkappaBalpha-dependent nuclear export of NF-kappaB (Karin and Ben-Neriah 2000). Here, we review the process of signal-induced IkappaB ubiquitination and degradation by comparing the degradation of several IkappaBs and discussing the characteristics of IkappaBs' ubiquitin machinery.
NF-κB 激活的关键步骤是 NF-κB 二聚体从其抑制蛋白中释放出来,这是通过 IkappaB 的蛋白水解实现的。这种不可逆的信号转导步骤构成了转录激活的承诺。该信号最终通过 NF-κB 的核排出而终止,这是基于 IkappaBalpha 转录、合成和 IkappaBalpha 依赖性 NF-κB 核输出的负反馈环的结果 (Karin 和 Ben-Neriah 2000)。在这里,我们通过比较几种 IkappaB 的降解并讨论 IkappaB 的泛素机制的特点,来回顾信号诱导的 IkappaB 泛素化和降解的过程。