Alteration of the stability of Bag-1 protein in the control of olfactory neuronal apoptosis

Normal apoptosis occurs continuously in the olfactory neuroepithelium of ad ult vertebrates, making it a useful model for studying neuronal apoptosis, Here we demonstrate that overexpression of the anti-apoptotic Bag1 gene in olfactory neuronal cells confers a strong resistance to apoptosis, Converse ly decreased levels of Bag1 were found to precede a massive wave of olfacto ry neuronal apoptosis triggered by synaptic target ablation, We show that t he decrease is brought about by ubiquitination and subsequent degradation o f the Bag-1 protein. The ring finger protein Siah-2 is a likely candidate f or the ubiquitination reaction since Siah-2 mRNA accumulated in lesioned ol factory neuroepithelium and overexpression of Siah-2 stimulated Bag-1 ubiqu itination and degradation in transient expression assays. These results tog ether identify destabilization of Bag-1 as a necessary step in olfactory ne uronal apoptosis.