Grassilli E, Benatti F, Dansi P, Giammarioli A M, Malorni W, Franceschi C, Desiderio M A
Department of Biomedical Sciences, University of Modena, Italy.
Biochem Biophys Res Commun. 1998 Sep 18;250(2):293-7. doi: 10.1006/bbrc.1998.9291.
We have previously shown that polyamine levels rapidly decrease in thymocytes undergoing apoptosis, and that ornithine decarboxylase increases early but too transiently to maintain elevated polyamine levels. These data led us to suppose that a precocious ornithine decarboxylase degradation might be responsible for the imbalance of polyamine metabolism. Ornithine decarboxylase is known to be degraded by the cytosolic 26S proteasome that plays an essential role in thymocyte apoptosis. In this paper we demonstrate that the inhibition of proteasome function preserves ornithine decarboxylase activity and prevents thymocytes from undergoing apoptosis after dexamethasone treatment. Since intracellular polyamine levels are also preserved, ornithine decarboxylase seems to be functionally active in maintaining polyamine homeostasis after proteasome inhibition in thymocytes. Our proposed role for the proteasome in quiescent cells upon an apoptotic stimulus is to degrade proteins like ornithine decarboxylase that are involved in the control of the cell cycle and cell survival.
我们之前已经表明，在经历凋亡的胸腺细胞中多胺水平会迅速下降，并且鸟氨酸脱羧酶虽早期增加但过于短暂，无法维持多胺水平的升高。这些数据使我们推测，鸟氨酸脱羧酶的过早降解可能是多胺代谢失衡的原因。已知鸟氨酸脱羧酶会被胞质26S蛋白酶体降解，而该蛋白酶体在胸腺细胞凋亡中起重要作用。在本文中，我们证明蛋白酶体功能的抑制可保留鸟氨酸脱羧酶活性，并防止胸腺细胞在用地塞米松处理后发生凋亡。由于细胞内多胺水平也得以保留，在蛋白酶体抑制后，鸟氨酸脱羧酶似乎在维持胸腺细胞多胺稳态方面具有功能活性。我们提出，在凋亡刺激下蛋白酶体在静止细胞中的作用是降解参与细胞周期和细胞存活控制的蛋白质，如鸟氨酸脱羧酶。
