The cullin-4 scaffold protein can assemble into differentially composed and highly dynamic CRL4 protein complexes that control the ubiquitin/proteasome-mediated degradation of many cellular substrate proteins. Bacher et al. (e00081-21) identify the kinase MEKK1 as a new interactor of CRL4 complexes. They further reveal the relevance of MEKK1 kinase activity for autoubiquitination of the CRL4 complex by differentially composed ubiquitin chains that contribute to DNA damage-induced degradation of CRL4 target proteins and cell survival. These data contribute to the understanding of the function of cullin-4, either as a frequently used ligand for proteolysis-targeting chimeras (PROTACs) or as a driver of tumorigenesis.

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本期重要文章

cullin-4 支架蛋白可以组装成差异组成和高度动态的 CRL4 蛋白复合物，控制泛素/蛋白酶体介导的许多细胞底物蛋白的降解。巴赫等人。(e00081-21) 将激酶 MEKK1 鉴定为 CRL4 复合物的新相互作用物。他们进一步揭示了 MEKK1 激酶活性与 CRL4 复合物自泛素化的相关性，差异组成的泛素链有助于 DNA 损伤诱导的 CRL4 靶蛋白降解和细胞存活。这些数据有助于了解 cullin-4 的功能，无论是作为蛋白水解靶向嵌合体 (PROTAC) 的常用配体还是作为肿瘤发生的驱动因素。