信号诱导的IκBα降解：与NF-κB的关联以及IκBα中的PEST序列并非必需。
Signal-induced degradation of I(kappa)B(alpha): association with NF-kappaB and the PEST sequence in I(kappa)B(alpha) are not required.
作者信息
Van Antwerp D J, Verma I M
机构信息
Laboratory of Genetics, The Salk Institute, San Diego, California 92186, USA.
出版信息
Mol Cell Biol. 1996 Nov;16(11):6037-45. doi: 10.1128/MCB.16.11.6037.
Abstract
Signal-induced degradation of I(kappa)B(alpha) via the ubiquitin-proteasome pathway requires phosphorylation on residues serine 32 and serine 36 followed by ubiquitination on lysines 21 and 22. We investigated the role of other regions of I(kappa)B(alpha) which may be involved in its degradation. Here we report that the carboxy-terminal PEST sequence is not required for I(kappa)B(alpha) signal-induced degradation. However, removal of the PEST sequence stabilizes free I(kappa)B(alpha) in unstimulated cells. We further report that a PEST deletion mutant does not associate well with NF-(kappa)B proteins but is degraded in response to signal. Therefore, we conclude that both association with NF-(kappa)B and a PEST sequence are not required for signal-induced I(kappa)B(alpha) degradation. Additionally, the PEST sequence may be required for constitutive turnover of free I(kappa)B(alpha).
摘要
通过泛素-蛋白酶体途径，信号诱导的IκBα降解需要丝氨酸32和丝氨酸36残基磷酸化，随后赖氨酸21和22发生泛素化。我们研究了IκBα其他可能参与其降解的区域的作用。在此我们报告，IκBα信号诱导的降解不需要羧基末端的PEST序列。然而，去除PEST序列可使未受刺激细胞中的游离IκBα稳定。我们进一步报告，PEST缺失突变体与NF-κB蛋白结合不佳，但在信号响应中会被降解。因此，我们得出结论，信号诱导的IκBα降解既不需要与NF-κB结合，也不需要PEST序列。此外，PEST序列可能是游离IκBα组成型周转所必需的。
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