INHIBITION OF PROTEASOME FUNCTION PREVENTS THYMOCYTE APOPTOSIS - INVOLVEMENT OF ORNITHINE DECARBOXYLASE

We have previously shown that polyamine levels rapidly decrease in thy mocytes undergoing apoptosis, and that ornithine decarboxylase increas es early but too transiently to maintain elevated polyamine levels. Th ese data led us to suppose that a precocious ornithine decarboxylase d egradation might be responsible for the imbalance of polyamine metabol ism. 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 fro m undergoing apoptosis after dexamethasone treatment, Since intracellu lar 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 proteas ome in quiescent cells upon an apoptotic stimulus is to degrade protei ns like ornithine decarboxylase that are involved in the control of th e cell cycle and cell survival. (C) 1998 Academic Press.