L-DNase II, a molecule that links proteases and endonucleases in apoptosis, derives from the ubiquitous serpin leukocyte elastase inhibitor.
The most widely recognized biochemical change associated with the majority of apoptotic systems is the degradation of genomic DNA. Among the enzymes that may participate in this cleavage, the acidic cation-independent DNase II is a likely candidate since it is activated in many apoptotic cells. To better understand its role, we purified and sequenced a DNase II extracted from porcine spleen. Protein sequencing of random peptides demonstrated that this enzyme is derived from a ubiquitous serpin, the leukocyte elastase inhibitor (LEI), by an acidic-dependent posttranslational modification or by digestion with elastase. We call this novel enzyme L-DNase II. In vitro experiments with purified recombinant LEI show that the native form has no effect on purified nuclei whereas its posttranslationally activated form induces pycnosis and DNA degradation. Antibodies directed against L-DNase II showed, in different cell lines, an increased expression and a nuclear translocation of this enzyme during apoptosis. Since the appearance of the endonuclease activity results in a loss of the anti-protease properties of LEI, the transformation from LEI to L-DNase II may act as a switch of protease and nuclease pathways, each of which is activated during apoptosis.
Torriglia
A
A
Développement, pathologie et vieillissement de la rétine, Unité 450 INSERM, affiliée CNRS, Association Claude Bernard, 75016 Paris, France. torrigli@infobiogen.fr
Perani
P
P
Brossas
J Y
JY
Chaudun
E
E
Treton
J
J
Courtois
Y
Y
Counis
M F
MF
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D013552:Swine
D015843:Serpins; D004706:Endodeoxyribonucleases; D004720:Endonucleases; C019329:deoxyribonuclease II; D010450:Endopeptidases