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.
Alteration of the stability of Bag-1 protein in the control of olfactory neuronal apoptosis
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T. Sourisseau, C. Desbois, L. Debure, D.D. Bowtell, A.C. Cato, J. Schneikert, E. Moyse, D. Michel; Alteration of the stability of Bag-1 protein in the control of olfactory neuronal apoptosis. J Cell Sci 1 April 2001; 114 (7): 1409–1416. doi: https://doi.org/10.1242/jcs.114.7.1409
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