Characterization of splice variants of human caspase-activated DNase with CIDE-N structure and function.
Internucleosomal DNA fragmentation is an apoptotic event that depends on the activity of different nucleases. Among them, the DNA fragmentation factor B, better known as caspase-activated DNase (CAD), is mainly responsible for this DNA fragmentation in dying cells. CAD is an endonuclease that is chaperoned and inhibited by inhibitor of CAD (ICAD). Activation of CAD needs the cleavage of ICAD by activated caspase-3. During the characterization of the staurosporine-induced apoptotic process in human neuroblastoma cell lines, we have found three novel splice variants of CAD. In all three messengers, the open reading frame is truncated after the second exon of the CAD gene. This truncated open reading frame codifies the CAD protein amino terminal part corresponding to the cell death-inducing DFF45-like effector-N (CIDE-N) domain. We have detected these splicing variants in human tissues and in peripheral white blood cells from 10 unrelated individuals, and their products have been showed to be expressed in certain mouse tissues. We demonstrate that these truncated forms of CAD are soluble proteins that interact with ICAD. We also provided evidences that these CIDE-N forms of CAD promote apoptosis in a caspase-dependent manner.
Bayascas
José R
JR
Grup de Senyalització Cel.lular i Apoptosi, Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, 25008 Lleida, Spain.
Yuste
Víctor J
VJ
Solé
Carme
C
Sánchez-López
Isabel
I
Segura
Miquel F
MF
Perera
Remei
R
Comella
Joan X
JX
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D053938:DNA Fragmentation; D003851:Deoxyribonucleases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014158:Transcription, Genetic
D051017:Apoptosis Regulatory Proteins; D010446:Peptide Fragments; D020033:Protein Isoforms; D011506:Proteins; D011994:Recombinant Proteins; C109664:caspase-activated DNase inhibitor; D003851:Deoxyribonucleases; C109663:caspase-activated deoxyribonuclease; D020169:Caspases