Overexpression of the chromosome 21 transcription factor Ets2 induces neuronal apoptosis.
Down syndrome (trisomy 21) neurons display an increased rate of apoptosis in vitro. The genes on chromosome 21 that mediate this increased cell death remain to be elucidated. Here we show that the chromosome 21 transcription factor Ets2, a gene that is overexpressed in Down syndrome, is expressed in neurons, and that moderate overexpression of Ets2 leads to increased apoptosis of primary neuronal cultures from Ets2 tg mice that involves activation of caspase-3. Our data therefore suggest that overexpression of ETS2 may contribute to the increased rate of apoptosis of neurons in Down syndrome.
Wolvetang
E J
EJ
Monash Institute of Reproduction and Development, Monash University, Monash Medical Center, 246 Clayton Road, 3168 Clayton, Australia. ernst.wolvetang@med.monash.edu.au
Bradfield
O M
OM
Hatzistavrou
T
T
Crack
P J
PJ
Busciglio
J
J
Kola
I
I
Hertzog
P J
PJ
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics*; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004268:DNA-Binding Proteins; D004314:Down Syndrome / Q000235:genetics* / Q000378:metabolism; D005333:Fetus; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors; D015854:Up-Regulation / Q000235:genetics
D017304:Annexin A5; D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494069:ETS2 protein, human; C494070:Ets2 protein, mouse; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases