Mechanism of action of developmentally regulated sea urchin inhibitor of eIF-4.
Mechanism of action of developmentally regulated sea urchin inhibitor of eIF-4.
复制标题
eIF-4 发育调控海胆抑制剂的作用机制。
DOI：
10.1002/dvg.1020140603
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Rhoads,RE
中科院分区：
文献类型：
--
作者：
Jagus,R;Huang,W;Hiremath,LS;Stern,BD;Rhoads,RE
The developmentally regulated inhibitor of eIF‐4 function found in unfertilized sea urchin eggs has been partially purified and its mechanism of action studied in vitro using purified recombinant eIF‐4α and cell‐free translation systems. The results demonstrate that although the phosphorylation of eIF‐4α is necessary to promote protein synthesis, it is not sufficient to maintain all aspects of eIF‐4 function. The egg inhibitor does not change eIF‐4α phosphorylation state. During the blockage of initiation caused by the egg inhibitor, eIF‐4α remains phosphorylated but accumulates in a 48S initiation intermediate. This suggests that the egg inhibitor functions by preventing the release of eIF‐4α from the small ribosomal subunit. The characteristics of the inhibitor in a reticulocyte translation system demonstrate that eIF‐4 activity is inhibited within 3–6 min. However, the inhibitor's characteristics in a mRNA‐dependent translation system contrast with this. Preincubation with the inhibitor for 5–25 min prior to the addition of mRNA does not prevent endogenous eIF‐4 from participating in translation but diminishes its ability to be reutilized, consistent with the accumulation of eIF‐4α on the small ribosomal subunit. The ribosomal localization of the inhibitor suggests that it could prevent eIF‐4α release by direct binding. The gradual inactivation of the inhibitor following fertilization indicates that it represents a component of a novel regulatory cascade that modulates eIF‐4 activity. © 1993 Wiley‐Liss, Inc.
