Identification of a novel ionizing radiation-induced nuclease, AEN, and its functional characterization in apoptosis.
To investigate ionizing radiation response, we screened genes that exhibit higher expression following gamma irradiation. We report here the isolation and functional characterization of a novel ionizing radiation-induced gene, AEN. Sequence analysis of AEN revealed exonuclease domain highly similar to that of exonuclease III. The AEN protein revealed DNase activity by cleaving various DNA substrates. Subcellular distribution of AEN exhibited nuclear colocalization with apoptotic nucleases such as CAD and AIF following irradiation. Moreover AEN distribution revealed perinuclear staining pattern which could be seen with other apoptotic nucleases. Irradiation of AEN-expressing cells resulted in synergistic increase of apoptosis whereas AEN deletion mutant in exonuclease domain did not. Our data, thus, suggest that radiation-induced AEN cleaves DNA in concert with other apoptotic nucleases and thereby enhances apoptosis following ionizing irradiation.
Lee
Ji-Hyun
JH
Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, Republic of Korea.
Koh
Yeon A
YA
Cho
Chul-Koo
CK
Lee
Su-Jae
SJ
Lee
Yun-Sil
YS
Bae
Sangwoo
S
D000595:Amino Acid Sequence; D017209:Apoptosis; D051033:Apoptosis Inducing Factor; D001483:Base Sequence; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000201:enzymology; D003851:Deoxyribonucleases / Q000032:analysis; D005090:Exodeoxyribonucleases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D005420:Flavoproteins / Q000032:analysis; D005720:Gamma Rays; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis; D008969:Molecular Sequence Data
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; C505243:AEN protein, human; D003851:Deoxyribonucleases; D005090:Exodeoxyribonucleases; C109663:caspase-activated deoxyribonuclease