Lyons R H
Department of Biological Chemistry and Reproductive Sciences, University of Michigan, Ann Arbor 48109-0404.
Mol Endocrinol. 1991 Dec;5(12):1897-902. doi: 10.1210/mend-5-12-1897.
The activity of nuclear factors can be regulated by blocking their ability to enter the nucleus, but how the cell achieves this is not yet understood. We demonstrate herein the serum-responsive nuclear localization of adenovirus E1a protein and show that this serum dependence is a property of the nuclear localization signal itself. When E1a protein is microinjected into the cytoplasm of cultured cells, it is found in the nucleus 30 min later only if the cells are serum fed; in serum-starved (growth-arrested) cells, the E1a is still cytoplasmic. Substituting the simian virus-40 T-antigen nuclear localization signal in place of the normal E1a signal abolishes this serum effect, and transferring the E1a signal to a heterologous protein also transfers the serum dependence. The serum effect on signal function is first exerted within 40 min after serum addition, suggesting that this is one of the earliest cellular responses to serum feeding. We conclude that the nuclear accumulation (and probably the function) of a protein is influenced not only by the presence of a nuclear localization signal, but also by the nature of that signal.
核因子的活性可通过阻断其进入细胞核的能力来调控，但细胞是如何做到这一点的，目前尚不清楚。我们在此证明了腺病毒E1a蛋白的血清反应性核定位，并表明这种血清依赖性是核定位信号本身的一种特性。当将E1a蛋白显微注射到培养细胞的细胞质中时，只有在细胞用血清处理的情况下，30分钟后才会在细胞核中发现它；在血清饥饿（生长停滞）的细胞中，E1a仍位于细胞质中。用猿猴病毒40 T抗原核定位信号取代正常的E1a信号可消除这种血清效应，将E1a信号转移到异源蛋白上也会转移血清依赖性。血清对信号功能的影响在添加血清后的40分钟内首次发挥作用，这表明这是细胞对血清处理最早的反应之一。我们得出结论，蛋白质的核积累（可能还有功能）不仅受核定位信号存在的影响，还受该信号性质的影响。
