Identification of FAM53C as a suppressive binding protein of a neurodevelopmental disorders-related kinase DYRK1A

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.21.537794v1?rss=1 Authors: Miyata, Y., Nishida, E. Abstract: A protein kinase DYRK1A encoded in human chromosome-21 is the major contributor for multiple symptoms observed in Down syndrome patients. In addition, DYRK1A dysfunction has been associated with various neuronal disorders, including autism spectrum disorder and Alzheimer disease. Here we identified FAM53C as a novel suppressive binding partner of DYRK1A. FAM53C bound to the catalytic kinase domain of DYRK1A, whereas DCAF7/WDR68, the major known DYRK1A-binding protein, binds to its N-terminal domain. The binding of FAM53C inhibited the protein kinase activity of DYRK1A to itself and an exogenous substrate MAPT/Tau. FAM53C did not bind directly to DCAF7/WDR68, whereas DYRK1A tethered FAM53C and DCAF7/WDR68 by binding concurrently to both of them. DYRK1A possesses a nuclear localization signal and accumulates in the nucleus when overexpressed in cells. FAM53C induced cytoplasmic re-localization of DYRK1A and DCAF7/WDR68. FAM53C is thus a binding suppressor of DYRK1A, anchoring it in an inactive state in the cytoplasm. The results explain for the first time why endogenous DYRK1A is distributed in the cytoplasm in the normal brain tissues. FAM53C-dependent regulation of DYRK1A may play a significant role in gene expression modification caused by DYRK1A. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC