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タイトル: | Identification of FAM53C as a cytosolic-anchoring inhibitory binding protein of the kinase DYRK1A |
著者: | Miyata, Yoshihiko ![]() ![]() ![]() Nishida, Eisuke |
著者名の別形: | 宮田, 愛彦 西田, 栄介 |
発行日: | Dec-2023 |
出版者: | Life Science Alliance, LLC |
誌名: | Life Science Alliance |
巻: | 6 |
号: | 12 |
論文番号: | e202302129 |
抄録: | The protein kinase DYRK1A encoded in human chromosome 21 is the major contributor to the multiple symptoms observed in Down syndrome patients. In addition, DYRK1A malfunction is associated with various other neurodevelopmental disorders such as autism spectrum disorder. Here, we identified FAM53C with no hitherto known biological function as a novel suppressive binding partner of DYRK1A. FAM53C is bound to the catalytic protein kinase domain of DYRK1A, whereas DCAF7/WDR68, the major DYRK1A-binding protein, binds to the N-terminal domain of DYRK1A. The binding of FAM53C inhibited autophosphorylation activity of DYRK1A and its kinase activity to 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, forming a tri-protein complex. DYRK1A possesses an NLS and accumulates in the nucleus when overexpressed in cells. Co-expression of FAM53C induced cytoplasmic re-localization of DYRK1A, revealing the cytoplasmic anchoring function of FAM53C to DYRK1A. Moreover, the binding of FAM53C to DYRK1A suppressed the DYRK1A-dependent nuclear localization of DCAF7/WDR68. All the results show that FAM53C binds to DYRK1A, suppresses its kinase activity, and anchors it in the cytoplasm. In addition, FAM53C is bound to the DYRK1A-related kinase DYRK1B with an Hsp90/Cdc37-independent manner. The results explain for the first time why endogenous DYRK1A is distributed in the cytoplasm in normal brain tissue. FAM53C-dependent regulation of the kinase activity and intracellular localization of DYRK1A may play a significant role in gene expression regulation caused by normal and aberrant levels of DYRK1A. |
記述: | ダウン症・自閉症関連タンパク質キナーゼDYRK1Aの抑制因子の発見 --FAM53Cタンパク質はDYRK1Aに結合して活性を低下させる--. 京都大学プレスリリース. 2023-11-24. Moderation surpasses excess: Protein-protein interaction discovery unveils Down syndrome's molecular mechanism potential. 京都大学プレスリリース. 2023-12-20. |
著作権等: | © 2023 Miyata and Nishida This article is available under a Creative Commons License (Attribution 4.0 International). |
URI: | http://hdl.handle.net/2433/286176 |
DOI(出版社版): | 10.26508/lsa.202302129 |
PubMed ID: | 37802655 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2023-11-24-0 https://www.kyoto-u.ac.jp/en/research-news/2023-12-20-0 |
出現コレクション: | 学術雑誌掲載論文等 |
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