L-DNase II: a new link in apoptotic pathways

Induction of apoptosis is triggered by the release of mitochondrial molecul es, followed by the activation of proteases and endonucleases. In this mole cular pathway, the activation of proteases known as caspases is thought to be the no-return step of apoptosis. Activation of endonucleases is believe to have a degradative function and to occur downstream of proteases. In neu ral apoptosis occurring during embryonic development of the chick retina an d in lens cell terminal differentiation, we have shown the activation of an acid DNase. The molecular study of this enzyme, present in many tissues, h as shown that it is synthesized as a serpin, the leukocyte elastase inhibit or, a molecule displaying an anti-protease activity. After induction of apo ptosis a post-translational modification of LEI gives rise to L-DNase IT, a protein devoid of antiprotease activity but with an endonuclease activity. It is then possible that after induction of apoptosis the L-LEI-DNase II p athway acts as a switch triggering, at the same time, the activation of end onucleases by the appearance of L-DNase II in the cell, and the activation of protease by releasing their inhibition. In this apoptotic pathway the no -return step would be located at the LEI-L-DNase II transition, instead of been at the caspase level.