生物
转移酶
蓖麻毒素
激酶
分子生物学
核糖核酸
序列(生物学)
生物化学
细胞生物学
酶
基因
毒素
作者
Mihail S. Iordanov,David Pribnow,Jennifer L. Magun,Thanh Hoai Dinh,Jean A. Pearson,Steven Li Ye Chen,Bruce E. Magun
标识
DOI:10.1128/mcb.17.6.3373
摘要
Inhibition of protein synthesis per se does not potentiate the stress-activated protein kinases (SAPKs; also known as cJun NH 2 -terminal kinases [JNKs]).The protein synthesis inhibitor anisomycin, however, is a potent activator of SAPKs/JNKs.The mechanism of this activation is unknown.We provide evidence that in order to activate SAPK/JNK1, anisomycin requires ribosomes that are translationally active at the time of contact with the drug, suggesting a ribosomal origin of the anisomycin-induced signaling to SAPK/JNK1.In support of this notion, we have found that aminohexose pyrimidine nucleoside antibiotics, which bind to the same region in the 28S rRNA that is the target site for anisomycin, are also potent activators of SAPK/JNK1.Binding of an antibiotic to the 28S rRNA interferes with the functioning of the molecule by altering the structural interactions of critical regions.We hypothesized, therefore, that such alterations in the 28S rRNA may act as recognition signals to activate SAPK/JNK1.To test this hypothesis, we made use of two ribotoxic enzymes, ricin A chain and ␣-sarcin, both of which catalyze sequence-specific RNA damage in the 28S rRNA.Consistent with our hypothesis, ricin A chain and ␣-sarcin were strong agonists of SAPK/JNK1 and of its activator SEK1/MKK4 and induced the expression of the immediate-early genes c-fos and c-jun.As in the case of anisomycin, ribosomes that were active at the time of exposure to ricin A chain or ␣-sarcin were able to initiate signal transduction from the damaged 28S rRNA to SAPK/JNK1 while inactive ribosomes were not.
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