ein repertoire. Specifically, miR-133b directly impairs the expression of important antiapoptotic genes. We provide evidence for FAIM as a target of miR-133b. Originally discovered during a screen aiming to identify factors responsible for Fas/CD95 resistance in primary splenic B cells, FAIM has emerged as a highly conserved atypical regulator of DR-mediated apoptosis. At present, two major isoforms of FAIM have been described. The long isoform is present almost exclusively in neurons, whereas the short one displays a much broader expression pattern. Over-expression studies in neurons revealed a protective role of FAIM-L against TNFa- and FasLmediated apoptosis upstream of both caspase 8 and 3, and the ability of FAIM-S to promote neurite outgrowth by 
a mechanism involving activation of NF-kB. Noticeably, FAIM-L and -S share the same 39-UTR and miR-133b binding site, implying that both are subjected to post-transcriptional regulation by miR-133b. In fact, enriched presence of miR-133b was identified in the midbrain region, where it regulates the maturation and function of dopaminergic neurons. Based on this observation and the data provided here, it would be attractive to investigate the interplay between FAIM and miR-133b during DR-triggered apoptosis and neuron development in the midbrain. Importantly, FAIM positively influences the expression of central antiapoptotic cellular FLICE-like inhibitory protein in lymphocytes and hepatocytes in-vivo. Reduced levels of cFLIP would allow a get IMR-1 better physical interaction of procaspase 8 with Fas/CD95 thus leading to more pronounced caspase activation and probably enhanced apoptosis. To test whether this was also the case in miR-133b-transfected cells, cFLIP expression was analyzed. No significant difference of cFLIP between ctrl miR- and miR-133b-transfected cells could be observed at the mRNA or protein level. A possible explanation for this could be that generation of a knockout mouse leads to 23416332” complete absence of the deleted gene, whereas transient miR treatment merely results in a partial reduction ” of protein expression. Therefore, miR-133b-transfected cells might still contain sufficient FAIM to assure expression of cFLIP. As the first reported post-transcriptional regulator of FAIM and considering the high degree of conservation of miR-133b and FAIM across different species, the role of miR-133b during further biological processes should be a matter of future studies. In addition to FAIM, we could further pinpoint the expression of an important antiapoptotic enzyme as miR-133b-dependent by using global proteome quantification techniques. GSTP1 belongs to a family of enzymes responsible for detoxification and protection of cells from attack by reactive species. GSTP1 expression is highly elevated in many neoplastic tissues and has been implicated in resistance to apoptosis. GSTP1 was reported to regulate TNFa-triggered signaling through interaction with TNF receptor-associated factor 2. As a consequence of this interaction, activation of apoptosis signal-regulating kinase 1 is impaired, and TNFa-mediated apoptosis is strongly disturbed. Recently, miR-133a, a cognate molecule of miR133b, was reported to regulate the expression of GSTP1 in head and neck squamous cell carcinoma cells. MiR-133a and b differ only in one base pair at the 39- end of the molecules. This position is furthest away from the seed region, which is essential for miR:target interaction. Hence, it is likely that miR-133b, a
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