The ankyrin repeats but not the PEST-like sequences are required for signal-dependent degradation of IkappaBalpha.
The ankyrin repeats but not the PEST-like sequences are required for signal-dependent degradation of IkappaBalpha.
复制标题
IkappaBalpha 的信号依赖性降解需要锚蛋白重复序列，但不需要 PEST 样序列。
作者：
T. Aoki;Y. Sano;T. Yamamoto;J. Inoue
Rel/NFkappaB转录因子的核活性受到称为IkappaBalpha的抑制亚基从细胞质室严格调节。IkappaBalpha在肿瘤坏死因子α (TNFalpha)受体、白细胞介素-1受体或CD40的刺激下迅速磷酸化和降解。为了探索信号诱导IkappaBalpha耗损的分子机制，我们描绘了IkappaBalpha中tnfalpha诱导的IkappaBalpha磷酸化和快速降解所需的结构域。与之前的报道相反，存在于IkappaBalpha的羧基末端区域的类害虫序列在tnfalpha诱导的降解中是不可缺少的，但在信号独立的降解中可能是必需的，例如在仙人掌中，IkappaBalpha的果蝇同源物。此外，与Rel和RelA形成复合物所必需的锚蛋白重复序列是tnfalpha诱导的降解所必需的，这表明假定的IkappaB蛋白酶可以与IkappaBalpha与RelA复合物相互作用，或者可以识别锚蛋白重复序列的结构。我们的数据还表明，锚蛋白重复序列和pest样序列都不是tnfalpha诱导的磷酸化所必需的。
The nuclear activity of Rel/NFkappaB transcription factors is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called IkappaBalpha. IkappaBalpha is rapidly phosphorylated and degraded in response to the stimulation through tumor necrosis factor alpha (TNFalpha) receptor, interleukin-1 receptor or CD40. To explore the molecular mechanisms of signal-induced depletion of IkappaBalpha, we have delineated the domain in IkappaBalpha that is required for TNFalpha-induced phosphorylation and rapid degradation of IkappaBalpha. In contrast to the previous reports, the PEST-like sequences, which are present in the carboxyl-terminal region of IkappaBalpha, are demonstrated here to be dispensable for TNFalpha-induced degradation but could be required for signal-independent degradation, as in the case of Cactus, Drosophila homologue of IkappaB. Furthermore, the ankyrin repeats, which are essential for forming a complex with Rel and RelA, are required for TNFalpha-induced degradation suggesting that the putative IkappaB protease could interact with IkappaBalpha in complex with RelA or could recognize the structure of ankyrin repeats. Our data also indicate that neither the ankyrin repeats nor the PEST-like sequences, are essential for TNFalpha-induced phosphorylation.