Role of Unphosphorylated, Newly Synthesized I (cid:107) B (cid:98) in Persistent Activation of NF- (cid:107) B

Role of Unphosphorylated, Newly Synthesized I (cid:107) B (cid:98) in Persistent Activation of NF- (cid:107) B
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未磷酸化的新合成 I (cid:107) B (cid:98) 在 NF- (cid:107) B 持续激活中的作用

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发表时间:
1996
期刊:
影响因子:
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通讯作者:
Sankar Ghosh
Sankar Ghosh
中科院分区:
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作者:
H. Suyang;R. Phillips;I. Douglas;Sankar Ghosh

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用引起NF-(cid:107)B持续活化的诱导剂刺激导致NF-(cid:107)B抑制剂I(cid:107)B(cid:97)和I(cid:107)B(cid:98)降解。尽管I(cid:107)B(cid:97)快速重新合成和积累,但在这些条件下NF-(cid:107)B仍然被诱导。我们现在报告说,I(cid:107)B(cid:98)也在刺激的细胞中重新合成,并表现为非磷酸化蛋白。未磷酸化的I(cid:107)B(cid:98)与胞质溶胶中的NF-(cid:107)B形成稳定的复合物;然而,这种结合未能掩盖NF-(cid:107)B上的核定位信号和DNA结合结构域,并且I(cid:107)B(cid:98)-NF-(cid:107)B复合物进入细胞核。因此,在长时间刺激期间,I(cid:107)B(cid:98)似乎充当NF-(cid:107)B的伴侣,保护其免受I(cid:107)B(cid:97)的侵害,并允许其转运至细胞核。转录因子NF-(cid:107)B是一种普遍表达的转录因子,在大量转录因子的诱导表达中发挥重要作用
Stimulation with inducers that cause persistent activation of NF- (cid:107) B results in the degradation of the NF- (cid:107) B inhibitors, I (cid:107) B (cid:97) and I (cid:107) B (cid:98) . Despite the rapid resynthesis and accumulation of I (cid:107) B (cid:97) , NF- (cid:107) B remains induced under these conditions. We now report that I (cid:107) B (cid:98) is also resynthesized in stimulated cells and appears as an unphosphorylated protein. The unphosphorylated I (cid:107) B (cid:98) forms a stable complex with NF- (cid:107) B in the cytosol; however, this binding fails to mask the nuclear localization signal and DNA binding domain on NF- (cid:107) B, and the I (cid:107) B (cid:98) –NF- (cid:107) B complex enters the nucleus. It appears therefore that during prolonged stimulation, I (cid:107) B (cid:98) functions as a chaperone for NF- (cid:107) B by protecting it from I (cid:107) B (cid:97) and allowing it to be transported to the nucleus. The transcription factor NF- (cid:107) B is a ubiquitously expressed transcription factor that plays an important role in the induc- ible expression of a large number of