Alteration of the stability of Bag-1 protein in the control of olfactory neuronal apoptosis.
Normal apoptosis occurs continuously in the olfactory neuroepithelium of adult vertebrates, making it a useful model for studying neuronal apoptosis. Here we demonstrate that overexpression of the anti-apoptotic Bag-1 gene in olfactory neuronal cells confers a strong resistance to apoptosis. Conversely decreased levels of Bag-1 were found to precede a massive wave of olfactory neuronal apoptosis triggered by synaptic target ablation. We show that the decrease is brought about by ubiquitination and subsequent degradation of the Bag-1 protein. The ring finger protein Siah-2 is a likely candidate for the ubiquitination reaction since Siah-2 mRNA accumulated in lesioned olfactory neuroepithelium and overexpression of Siah-2 stimulated Bag-1 ubiquitination and degradation in transient expression assays. These results together identify destabilization of Bag-1 as a necessary step in olfactory neuronal apoptosis.
Sourisseau
T
T
Information et Programmation Cellulaire, UMR 6026 CNRS-Université de Rennes1, Campus de Beaulieu, Bat.13. 35042 Rennes cedex, France.
Desbois
C
C
Debure
L
L
Bowtell
D D
DD
Cato
A C
AC
Schneikert
J
J
Moyse
E
E
Michel
D
D
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D019556:COS Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins; D004298:Dopamine / Q000494:pharmacology; D015536:Down-Regulation; D015870:Gene Expression; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009687:Nuclear Proteins / Q000378:metabolism; D009831:Olfactory Mucosa / Q000166:cytology*; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000235:genetics; D015854:Up-Regulation; D000098563:Seven in Absentia Proteins
C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D014452:Ubiquitins; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D004298:Dopamine