Different mechanisms control signal-induced degradation and basal turnover of the NF-kappa B inhibitor I kappa B alpha in vivo
Different mechanisms control signal-induced degradation and basal turnover of the NF-kappa B inhibitor I kappa B alpha in vivo
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DOI：
10.1002/j.1460-2075.1996.tb01061.x
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发表时间：
1996-12-02
期刊：
影响因子：
11.4
通讯作者：
Scheidereit, C
中科院分区：
文献类型：
--
作者：
Krappmann, D;Wulczyn, FG;Scheidereit, C
The transcription factor NF-kappa B is sequestered in the cytoplasm by a family of I kappa B molecules. Upon cellular stimulation with diverse agents, one of these molecules, I kappa B alpha, is rapidly phosphorylated and subsequently degraded. This process triggers nuclear translocation of NF-kappa B and the successive activation of target genes. Independent of its rapid stimulation-induced breakdown, I kappa B alpha is inherently unstable and undergoes a continuous turnover. To compare the mechanisms and protein domains involved in inducible and basal degradation of I kappa B alpha in intact cells we employed a transfection strategy using tagged I kappa B alpha and ubiquitin molecules. We show that tumor necrosis factor alpha (TNF alpha) induced breakdown of I kappa B alpha but not its basal turnover coincides with ubiquitination in the aminoterminal signal response domain (SRD) of I kappa B alpha. Neither the SRD nor the carboxy-terminal PEST sequence is needed for basal turnover, which instead depends only on the core ankyrin repeat domain. Despite the differences in the requirements of protein domains and ubiquitin-conjugation for both degradation pathways, each one is mediated by the proteasome. This finding is important for understanding alternative modes of controlling NF-kappa B activity.
