Proline rich 7 (Prr7) is a transmembrane protein found in the postsynaptic density (PSD) of neurons in rat brains[1]. Prr7 contains a nuclear localization signal and can undergo cleavage and translocation to the nucleus (as a small fragment, deltaN). Previous work in our lab showed that NMDA (N-methyl-D-aspartate) receptor activation can trigger this translocation. This finding has cultivated the idea that Prr7 communicates synaptic events to the nucleus to regulate gene expression necessary for promoting long-term changes in synatic function. [2]Hrdinka et al., (2011) showed, that expression of Prr7 in Jurkat cells up-regulated the levels of the transcription factor, c-Jun. As of yet, it is unclear how Prr7 effects the level of c-Jun and what the exact effect is. In neurons, c-Jun levels are regulated by the F-box protein Fbw7g. Fbw7 is part of the SCF (Skp1-Cullin-F box) RING-type E3 ubiquitin ligase[3]. Interestingly, Prr7 contains a phosphodegron motif, which is recognized by Fbw7. In this study I aimed to identify how Prr7 regulates c-Jun protein levels by examining the interaction of Prr7 with Fbw7g. Using immunoctytochemistry and subsequent imaging, my data indicated that DeltaN Prr7 interacts with cJun and that deltaN Prr7 co-localizes with Fbw7g and c-Jun in HeLa cells. In addition, through immunoprecipitation and western blotting experiments, I found that DeltaN Prr7 along with the full length version of Prr7 protect c-Jun from ubiquitination by Fbw7g. I also tested this in neurons and found a decrease in levels of c-Jun when Prr7 was knocked down. Together, these results suggest that Prr7 acts as a novel synapse to nucleus messenger to regulate the ubiquitination levels of the transcription factor c-Jun, in neurons. [1] Jordan et al.,(2004) Identification and verification of novel rodent postsynaptic density proteins. Molecular Cell Proteomics.3(9):857-71.[2] Hrdinka et al., (2011) Prr7 is a transmembrane adaptor protein expressed in activated T-cells involved in regulation of T-cell receptor signaling and apoptosis. JBC 286(22):19617-29.[3] Nateri et al., (2004) The ubiquitin ligase SCFFbw7 antagonizes apoptotic JNK signaling. Science 303(5662)1374-8.

Prr7 is a novel regulator of the transcription factor, c-Jun, in neurons

247th National Meeting (2014)

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