Ubiquitin as a central cellular regulator.-猫眼课题宝

DOI：

10.1016/s0092-8674(03)00971-1

发表时间：

2004-01-23

期刊：

Cell

影响因子：

64.5

通讯作者：

中科院分区：

生物学1区

文献类型：

作者：

Finley, Daniel;Ciechanover, Aaron;Varshavsky, Alexander

60多年前，利用稳定同位素在体内标记蛋白质的研究表明，大多数蛋白质分子的存活时间与它们所处的细胞一样长（Schoenheimer，1942）。尽管有这些证据，但直到20世纪80年代，普遍的观点是细胞内蛋白质降解是一个简单甚至平凡的过程，主要用于处理“老化”或其他受损的蛋白质。细胞调节被认为是一个独立的事件，主要由基因表达的抑制因子和激活因子介导，通常被认为是长期存在的。这种不平衡的观点的原因之一是很难将溶酶体中长期公认的蛋白水解系统与细胞内调节的特定途径联系起来。因此，在20世纪60年代和70年代，大多数研究基因表达的人都认为他们所关心的调控回路不涉及短寿命蛋白质。正如我们现在所知道的，事实恰恰相反，特别是在真核生物中，许多转录调节因子是条件性短寿命蛋白质，其在细胞中的水平取决于其泛素依赖性蛋白水解的速率，至少与其合成速率一样多。虽然细胞内蛋白水解的功能的限制性前现代观点并不是每个人都认同的（参见，例如，Schimke和Doyle，1971; Poole等人，1978），但关于溶酶体外蛋白质降解重要性的确切证据不得不等到ts 85研究（Finley et al.，1984; Ciechanover等人，1984年）。泛蛋白是一种由76个残基组成的蛋白质，由G. Goldstein及其同事（Goldstein等人，1975），他在许多不同的生物体中发现了这种功能未知的蛋白质，并给它起了一个事后看来非常恰当的名字。1977年，第一个与组蛋白H2 A共价结合的泛素结合物被描述（Goldknopf和Busch，1977）。1978年，A. Hershko和他的研究生A. Ciechanover和Y. Hod报道了添加到兔网织红细胞提取物中的变性球蛋白的降解需要小的热稳定蛋白（Ciechanover等人，1978年）。1980年，Hershko、Ciechanover及其同事与I. Rose，证明了上述热稳定蛋白，

That most protein molecules do not last as long as the cell in which they reside was suggested more than 60 years ago, by studies that utilized stable isotopes to label proteins in vivo (Schoenheimer, 1942). Despite this evidence, the prevailing view, until the 1980s, was that intracellular protein degradation was a simple and even mundane process, serving largely to dispose of" aged" or otherwise damaged proteins. Cellular regulation was believed to be a separate affair, mediated primarily by repressors and activators of gene expression, which were assumed, often tacitly, to be long-lived. Among the reasons for this lopsided perspective was the difficulty of connecting the long-recognized proteolytic system in the lysosomes to specific pathways of intracellular regulation. Thus, most people studying gene expression in the 1960s and 1970s assumed that the regulatory circuits they cared about did not involve short-lived proteins. As we know now, just the opposite proved true, especially in eukaryotes, where many transcriptional regulators are conditionally short-lived proteins whose levels in a cell are determined by the rates of their ubiquitin-dependent proteolysis at least as much as by the rates of their synthesis. Although the constricting premodern view of the functions of intracellular proteolysis wasn't shared by everyone (see, for example, Schimke and Doyle, 1971; Poole et al., 1978), definitive evidence for the importance of extralysosomal protein degradation had to wait until the ts85 studies (Finley et al., 1984; Ciechanover et al., 1984). Ubiquitin, a 76 residue protein, was identified by G. Goldstein and colleagues (Goldstein et al., 1975), who detected this protein, of unknown function, in many different organisms, and gave it a name that in hindsight is remarkably apt. The first covalent ubiquitin conjugate, to histone H2A, was described in 1977 (Goldknopf and Busch, 1977). In 1978, A. Hershko and his graduate students A. Ciechanover and Y. Hod reported that a small heat-stable protein was required for the degradation of denatured globin added to rabbit reticulocyte extracts (Ciechanover et al., 1978). In 1980, Hershko, Ciechanover and colleagues, in a collaboration with I. Rose, demonstrated that the above heat-stable protein,

Ubiquitin as a central cellular regulator.

文献摘要

被引文献

相似文献