Identification of inhibitor-of-differentiation 2 (Id2) as a modulator of neuronal apoptosis.
Inhibitor-of-differentiation 2 (Id2) belongs to a family of transcriptional modulators that are characterized by a helix loop helix region but lack the basic amino acid domain. During development, Id2 antagonizes differentiation mediated by the retinoblastoma protein, probably by scavenging downstream E-box basic helix-loop-helix proteins. Here, using differential display RT-PCR, we identify Id2 as an induced gene during serum and potassium deprivation-induced apoptosis of cerebellar granule neurons. Consistent with a biological role for induced Id2 messenger RNA and protein expression in neuronal cell death, expression of Id2 antisense RNA, or targeted deletion of the Id2 gene in neurons from Id2 knock-out mice, protect from apoptosis. Further, gene transfer- mediated overexpression of Id2 induces neuronal cell death both in high potassium and low potassium conditions. Thus, the present study defines a role for Id2 in the modulation of neuronal apoptosis.
Gleichmann
M
M
Department of Neurology, University of Tübingen, Tübingen, Germany.
Buchheim
G
G
El-Bizri
H
H
Yokota
Y
Y
Klockgether
T
T
Kügler
S
S
Bähr
M
M
Weller
M
M
Schulz
J B
JB
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D051797:Inhibitor of Differentiation Protein 2; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010957:Plasmids; D011188:Potassium / Q000378:metabolism; D016372:RNA, Antisense / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; C497451:Id2 protein, rat; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D016372:RNA, Antisense; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D011188:Potassium