Gene knockouts of c-src, transforming growth factor beta 1, and tenascin suggest superfluous, nonfunctional expression of proteins.
Gene knockouts of c-src, transforming growth factor beta 1, and tenascin suggest superfluous, nonfunctional expression of proteins.
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DOI：
10.1083/jcb.120.5.1079
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发表时间：
1993-03
影响因子：
7.8
通讯作者：
Erickson, H P
中科院分区：
文献类型：
--
作者：
Erickson, H P
基因靶向技术仍处于起步阶段，但一个令人惊讶的主题正在反复出现。一个被认为重要的基因的破坏通常会产生最小的表型。在某些情况下，在一个意想不到的组织中发现了一种表型，但没有破坏蛋白质最高表达的组织，以及它的功能被认为是最重要的组织。一种常见的解释是，蛋白质是“冗余的”，也就是说，具有重复功能的密切相关的蛋白质可能会填补被淘汰的蛋白质。然而，单词冗余也可以用来表示多余的，这可能是更合适的意义。具有重复功能的蛋白质的共表达可能是多余和浪费的，但是，正如下面所讨论的，是可以容忍的。关于多余表达的更极端的观点是，蛋白质可能在根本没有功能的细胞或组织中显著表达。在过去的十年中，通过克隆或抗体发现了许多蛋白质，让研究人员确定其功能。对功能的研究通常从免疫细胞化学开始，以确定蛋白质表达的位置和时间。这种解释几乎是普遍的，即蛋白质在其最显著表达的位点起着重要作用。然而，如果蛋白质在没有功能的地方表达得过多，这些解释就需要重新评估。
H~ technology of gene targeting is still in its infancy, but one astonishing theme is being seen over and over. Disruption of a supposedly important gene frequently produces a minimal phenotype. In some cases a phenotype is discovered in an unexpected tissue, but there is no disruption of the tissues where the protein is most highly expressed, and where its function was thought to be most important. A frequent explanation is that proteins are" redundant," in the sense that closely related proteins with duplicated functions might fill in for the one eliminated. However, the word redundant can also be used to mean superfluous, and this may be the more appropriate sense. Coexpression of proteins with duplicated functions is probably superfluous and wasteful but, as argued below, may be tolerated. The more extreme view of superfluous expression is that proteins may be prominently expressed in cells or tissues where they have no function at all.Over the last decade many proteins have been discovered through cloning or antibodies, leaving the investigators to determine the function. The search for function frequently begins with immunocytochemistry, to determine where and when the protein is expressed. The interpretation, that the protein is playing an important role at the sites where it is most prominently expressed, is almost universal. If, however, proteins are expressed superfluously, where they have no function, these interpretations need to be re-evaluated.