AMINO-ACID-SEQUENCES COMMON TO RAPIDLY DEGRADED PROTEINS - THE PEST HYPOTHESIS

AMINO-ACID-SEQUENCES COMMON TO RAPIDLY DEGRADED PROTEINS - THE PEST HYPOTHESIS
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DOI:
10.1126/science.2876518
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发表时间:
1986-10-17
期刊:
影响因子:
56.9
通讯作者:
RECHSTEINER, M
RECHSTEINER, M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
ROGERS, S;WELLS, R;RECHSTEINER, M

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十个蛋白质的氨基酸序列少于2小时,含有一个或多个富含脯氨酸(P),谷氨酸(E),丝氨酸(S)和苏氨酸(T)的区域。这些害虫区域通常是(但并非总是),两侧是包含几个带正电氨基酸的簇。对35种细胞内半衰期20至220小时的35种蛋白质的类似检查表明,只有3个蛋白质包含害虫区域。根据这些信息,预计包含多个害虫序列的酪蛋白将在真核细胞内迅速降解。红细胞介导的125i标记的酪蛋白对HeLa细胞的显微注射的显微注射证实了这一预期,在那里它们表现出少于2小时的半衰期。注射的.alpha.-和.beta.-casein以及具有细胞内稳定性的害虫区域的逆相关性的快速降解表明,这些区域的存在可能导致含有它们的蛋白质的细胞内降解迅速。
The amino acid sequences of ten proteins with intracellular half-lives less than 2 hours contain one or more regions rich in proline (P), glutamic acid (E), serine (S), and threonine (T). These PEST regions are generally, but not always, flanked by clusters containing several positively charged amino acids. Similar inspection of 35 proteins with intracellular half-lives between 20 and 220 hours revealed that only three contain a PEST region. On the basis of this information, it was anticipated that caseins, which contain several PEST sequences, would be rapidly degraded within eukaryotic cells. This expectation was confirmed by red blood cell-mediated microinjection of 125I-labeled caseins into HeLa cells where they exhibited half-lives of less than 2 hours. The rapid degradation of injected .alpha.- and .beta.-casein as well as the inverse correlation of PEST regions with intracellular stability indicate that the presence of these regions can result in the rapid intracellular degradation of the proteins containing them.