2012). 14-3-3 proteins regulate
phosphorylation-mediated cell signaling kinase inhibitor Tofacitinib including MAPK pathways; thus, Sepw1 may function in signal transduction from receptors to target proteins via reactive oxygen intermediates. High muscle expression of Sepw1 mRNA is associated with myoblasts, and expression is decreased in differentiated myotubes (Loflin et al. 2006). Thus, the abundance of Sepw1 mRNA and protein in postmitotic neurons is mysterious. Sepw1 mRNA is widely expressed in neurons, including apparent expression in axonal and dendritic compartments [(Willis et al. 2005, 2007; Taylor et al. 2009; Cajigas et al. 2012) supplemental data]. Whether sellekchem translation of Sepw1 occurs in these Inhibitors,research,lifescience,medical distal cellular compartments is uncertain. Selenoprotein translation in mammals specifically requires the proteins Sbp2 and EFSec, in addition to the standard translation machinery. Both of these proteins were identified in synaptosomes along with Sps2 Inhibitors,research,lifescience,medical and Scly, which are important in Sec metabolism. The major protein involved in selenoprotein translation that was not investigated in this study is the Sec-synthetase enzyme, SepSecS. SepSecS, also known as soluble liver antigen/liver pancreas antigen, is required to generate the
Sec-loaded tRNASec (Palioura et al. 2010). We were unable to test for the presence of SepSecS in synaptosomes. However, given the proteins identified in Inhibitors,research,lifescience,medical synaptosomes, synthesis of Sepw1 at or near synapses appears to be plausible. Selenoprotein Inhibitors,research,lifescience,medical mRNAs are thought to be packaged into mRNP complexes, which aid in preventing nonsense codon-mediated decay (NMD) of transcripts with a Sec-specifying UGA that could be interpreted as a premature termination codon. Staufen proteins Stau1 and Stau2 are involved
in a related process termed Staufen-mediated Inhibitors,research,lifescience,medical decay (Park et al. 2013), and we have shown that Sepw1 mRNA associates with Stau2 in SH-SY5Y cells. This finding is supported by data showing that Sepw1 mRNA is found in Stau2-mRNP complexes in both HEK293 cells and embryonic rat brains ([Maher-Laporte and DesGroseillers 2010] supplemental data). Stau2 is particularly abundant in brain and contributes to dendritic transcript localization and translational regulation (Duchaine et al. 2002; Mikl et al. 2011). Here, Cilengitide we demonstrate that Sepw1 is highly expressed in brain and synapses, and suggest that its translation is under control of RNA-binding proteins such as Stau2. In addition to Stau2, DJ-1/Park7 has been experimentally demonstrated to coimmunoprecipitate with Sepw1 mRNA in M17 human neuroblastoma cells and human brain tissue (van der Brug et al. 2008; Blackinton et al. 2009). DJ-1 is a multifunctional redox-sensitive protein that is associated with Parkinson’s disease, stroke, and cancer (Kahle et al. 2009). DJ-1 protein has shown varying degrees of localization to synapses, axons, and dendrites (Olzmann et al. 2007; Usami et al. 2011), further suggesting the local regulation of Sepw1 expression in distal neuronal compartments.