CENTRAL OF I-KAPPA-B-ALPHA PROTEOLYSIS BY SITE-SPECIFIC, SIGNAL-INDUCED PHOSPHORYLATION
CENTRAL OF I-KAPPA-B-ALPHA PROTEOLYSIS BY SITE-SPECIFIC, SIGNAL-INDUCED PHOSPHORYLATION
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DOI：
10.1126/science.7878466
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发表时间：
1995-03-10
期刊：
影响因子：
56.9
通讯作者：
SIEBENLIST, U
中科院分区：
文献类型：
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作者：
BROWN, K;GERSTBERGER, S;SIEBENLIST, U
I κ B-α通过将转录因子NF-κ B保留在细胞质中来抑制它。各种刺激，通常是与压力或病原体有关的刺激，迅速激活κ B-α。这释放NF-κ B以易位到细胞核并启动对生物体防御重要的基因的转录。NF-κ B的活化与I κ B-α的磷酸化相关，并且需要该抑制剂的蛋白水解。当I κ B-α的丝氨酸-32或丝氨酸-36发生突变时，蛋白质不经历信号诱导的磷酸化或降解，NF-κ B不能被激活。这些结果表明，在这些残基中的一个或两个的磷酸化对于NF-κ B的活化是至关重要的。
I kappa B-alpha inhibits transcription factor NF-kappa B by retaining it in the cytoplasm. Various stimuli, typically those associated with stress or pathogens, rapidly inactivate I kappa B-alpha. This liberates NF-kappa B to translocate to the nucleus and initiate transcription of genes important for the defense of the organism. Activation of NF-kappa B correlates with phosphorylation of I kappa B-alpha and requires the proteolysis of this inhibitor. When either serine-32 or serine-36 of I kappa B-alpha was mutated, the protein did not undergo signal-induced phosphorylation or degradation, and NF-kappa B could not be activated. These results suggest that phosphorylation at one or both of these residues is critical for activation of NF-kappa B.