Guiochon-Mantel A, Delabre K, Lescop P, Milgrom E
Institut National de la Santé et de la Recherche Médicale, Unité 135, Hormones et Reproduction, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7179-83. doi: 10.1073/pnas.91.15.7179.
Several nuclear proteins, including steroid hormone receptors, have been shown to shuttle continuously between the nucleus and the cytoplasm. The mechanism of entry of proteins into the nucleus is well documented, whereas the mechanism of their outward movement into the cytoplasm is not understood. We have grafted the nuclear localization signals of the progesterone receptor or the simian virus 40 large tumor antigen onto beta-galactosidase. These additions were shown to impart to the protein the ability to shuttle between the nucleus and the cytoplasm. Microinjected proteins devoid of a nuclear localization signal were unable to exit from the nucleus. The same nuclear localization signals are thus involved in both the inward and the outward movement of proteins through the nuclear membrane. We also show that although the nuclear import requires energy, the nuclear export does not. These results suggest that the nucleocytoplasmic shuttling may be a general phenomenon for nuclear proteins that could possibly undergo modifications in the cytoplasm and exert some biological activities there. These conclusions also imply that at least part of the cellular machinery involved in the nuclear import of proteins may function bidirectionally.
包括类固醇激素受体在内的几种核蛋白已被证明可在细胞核与细胞质之间持续穿梭。蛋白质进入细胞核的机制已有充分记录，而它们向外进入细胞质的机制尚不清楚。我们已将孕酮受体或猿猴病毒40大肿瘤抗原的核定位信号嫁接到β-半乳糖苷酶上。结果表明，这些添加物赋予了蛋白质在细胞核与细胞质之间穿梭的能力。微注射缺乏核定位信号的蛋白质无法从细胞核中排出。因此，相同的核定位信号参与了蛋白质通过核膜的向内和向外移动。我们还表明，尽管核输入需要能量，但核输出则不需要。这些结果表明，核质穿梭可能是核蛋白的普遍现象，这些核蛋白可能在细胞质中发生修饰并在那里发挥一些生物学活性。这些结论还意味着，参与蛋白质核输入的细胞机制至少有一部分可能双向发挥作用。
