Aminodipeptidase inhibitor-induced cell death in quiescent lymphocytes: A review

We recently isolated and cloned an intracellular post-proline cleaving amin odipeptidase, quiescent cell proline dipeptidase (QPP), which has a substra te specificity very similar to that of dipeptidyl peptidase IV (CD26/DPPIV) . Highly specific inhibitors of proline aminodipeptidases activate a novel apoptotic pathway in quiescent lymphocytes. The target of these inhibitors is not CD26/DPPIV, but appears to be QPP. The apoptosis pathway induced by the aminodipeptidase inhibitors is unusual in that it is restricted to quie scent lymphocytes, but not activated or transformed lymphocytes. The caspas es activated in this apoptotic pathway are different from those activated i n Fas or gamma-irradiation mediated cell death pathways, and furthermore, t he proteasome appears to play a role in this death pathway. A large number of signal molecules including chemokines and cytokines have a highly conser ved X-Pro motif on the N-terminus, rendering them potential substrates of Q PP and players in the survival of resting lymphocytes.