ABSTRACT
In previous studies, we found interferon-a (IFN-a) could reduce protein levels of p11, 5-hydroxytryptamine receptor 1b(5-HT1b) and 5-hydroxytryptamine receptor 4 (5-HT4), but does not influence their messenger RNA levels in SH-sy5ycells. Thus, we investigated the post-transcriptional modulation of these molecules by IFN-a. SH-sy5y cells were treatedwith IFN-a, NH4Cl or MG132 alone or in combination, and then the protein levels of p11, 5-HT1b and 5-HT4 wereanalyzed by western blots. The regulatory effects of p11 on 5-HT1b and 5-HT4 were also determined in p11 knock-downcells. NH4Cl but not MG132 could reverse the protein level of p11 in IFN-a-treated SH-sy5y cells. MG132 could recoverthe protein levels of 5-HT1b and 5-HT4 in p11 knock-down cells. The down-regulation effects of IFN-a on p11, 5-HT1band 5-HT4 were associated with the lysosome and ubiquitin–proteasome-mediated pathways. p11 was identified as a potentregulator to modulate the ubiquitination of 5-HT1b and 5-HT4. Therefore, it could be potential target therapies in IFN-ainduced depression.