ECE2019 Poster Presentations Adrenal and Neuroendocrine Tumours 1 (60 abstracts)
Pohang University of Science and Technology, Pohang, Republic of Korea.
The misfolded proteins with abnormal polyglutamine (polyQ) expansion cause neurodegenerative disorders including Huntingtons disease (HD). Recently, Vaccinia-related kinase 2 (VRK2) were found to accumulate polyQ aggregates by controlling TCP-1 ring complex (TRiC)/Chaperonin-containing TCP-1 (CCT), which has an essential role in preventing against the aggregation and cytotoxicity of polyQ proteins. Interestingly, VRK2 expression is known to be much higher in actively proliferating cells, but is maintained at a low level in the brain via unknown mechanism. Here we found that neuronal cell-specific basal level of VRK2 is regulated by post-transcriptional regulation rather than the regulation in transcription itself. Moreover, heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) specifically binds to 3UTR of VRK2 mRNA in neuronal cells and reduces its mRNA stability. In relation to that we found a dramatic decrease in CCT4 protein level due to a reduction in hnRNP Q, followed by an increase in polyQ aggregation. Taken together, these studies could provide new insights into how neuronal hnRNP Q regulates VRK2 mRNA stability and contributes to HD prevention, and open new prognostic marker of HD.