Maekawa Masashi, Higashiyama Shigeki
Division of Cell Growth and Tumor Regulation, Proteo-Science Center, Ehime University, Shitsukawa, Toon, Ehime, 791-0295, Japan.
Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
Bioessays. 2020 Aug;42(8):e1900256. doi: 10.1002/bies.201900256. Epub 2020 Jun 2.
Protein ubiquitination constitutes a post-translational modification mediated by ubiquitin ligases whereby ubiquitinated substrates are degraded through the proteasomal or lysosomal pathways, or acquire novel molecular functions according to their "ubiquitin codes." Dysfunction of the ubiquitination process in cells causes various diseases such as cancers along with neurodegenerative, auto-immune/inflammatory, and metabolic diseases. KCTD10 functions as a substrate recognition receptor for cullin-3 (CUL3), a scaffold protein in RING-type ubiquitin ligase complexes. Recently, studies by ourselves and others have identified new substrates that are ubiquitinated by the CUL3/KCTD10 ubiquitin ligase complex. Moreover, the type of polyubiquitination (e.g., K27-, K48-, or K63-chain) of various substrates (e.g., RhoB, CEP97, EIF3D, and TRIF) mediated by KCTD10 underlies its divergent roles in endothelial barrier formation, primary cilium formation, plasma membrane dynamics, cell proliferation, and immune response. Here, the physiological functions of KCTD10 are summarized and potential mechanisms are proposed.
蛋白质泛素化是一种由泛素连接酶介导的翻译后修饰，通过该修饰，泛素化底物可通过蛋白酶体或溶酶体途径降解，或根据其“泛素密码”获得新的分子功能。细胞中泛素化过程的功能障碍会导致各种疾病，如癌症以及神经退行性疾病、自身免疫/炎症性疾病和代谢性疾病。KCTD10作为cullin-3（CUL3）的底物识别受体发挥作用，CUL3是RING型泛素连接酶复合物中的一种支架蛋白。最近，我们和其他人的研究已经鉴定出被CUL3/KCTD10泛素连接酶复合物泛素化的新底物。此外，KCTD10介导的各种底物（如RhoB、CEP97、EIF3D和TRIF）的多聚泛素化类型（例如K27-、K48-或K63-链）是其在内皮屏障形成、初级纤毛形成、质膜动力学、细胞增殖和免疫反应中发挥不同作用的基础。在此，总结了KCTD10的生理功能并提出了潜在机制。
