Inhibition of proteasome function prevents thymocyte apoptosis: involvement of ornithine decarboxylase.
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.
Grassilli
E
E
Department of Biomedical Sciences, University of Modena, Italy.
Benatti
F
F
Dansi
P
P
Giammarioli
A M
AM
Malorni
W
W
Franceschi
C
C
Desiderio
M A
MA
D000818:Animals; D017209:Apoptosis; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
D009097:Multienzyme Complexes; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D009955:Ornithine Decarboxylase