Equal segregation of chromosomes during mitosis ensures euploidy of daughter cells. Defects in this process may result in an imbalance in the chromosomal composition and cellular transformation. Proteolytic and non‐proteolytic ubiquitylation pathways ensure directionality and fidelity of mitotic progression but specific mitotic functions of deubiquitylating enzymes (DUBs) remain less studied. Here we describe the role of the DUB ubiquitin carboxyl‐terminal hydrolase isozyme L3 (UCHL3) in the regulation of chromosome bi‐orientation and segregation during mitosis. Downregulation or inhibition of UCHL3 leads to chromosome alignment defects during metaphase. Frequent segregation errors during anaphase are also observed upon inactivation of UCHL3. Mechanistically, UCHL3 interacts with and deubiquitylates Aurora B, the catalytic subunit of chromosome passenger complex (CPC), known to be critically involved in the regulation of chromosome alignment and segregation. UCHL3 does not regulate protein levels of Aurora B or the binding of Aurora B to other CPC subunits. Instead, UCHL3 promotes localization of Aurora B to kinetochores, suggesting its role in the error correction mechanism monitoring bi‐orientation of chromosomes during metaphase. Thus, UCHL3 contributes to the regulation of faithful genome segregation and maintenance of euploidy in human cells.

中文翻译：

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去泛素化酶UCHL3调节有丝分裂过程中染色体的双向定向和分离

有丝分裂期间染色体的均等分离确保了子细胞的整倍性。这个过程中的缺陷可能导致染色体组成和细胞转化的不平衡。蛋白水解和非蛋白水解泛素化途径确保了有丝分裂进程的方向性和保真度，但去泛素化酶 (DUB) 的特定有丝分裂功能研究较少。在这里，我们描述了 DUB 泛素羧基末端水解酶同工酶 L3（UCHL3）在有丝分裂过程中调节染色体双向和分离中的作用。UCHL3 的下调或抑制导致中期染色体排列缺陷。在 UCHL3 失活时也观察到后期期间频繁的分离错误。从机制上讲，UCHL3 与 Aurora B 相互作用并去泛素化，染色体乘客复合体 (CPC) 的催化亚基，已知在染色体排列和分离的调节中至关重要。UCHL3 不调节 Aurora B 的蛋白质水平或 Aurora B 与其他 CPC 亚基的结合。相反，UCHL3 促进 Aurora B 定位到动粒，表明其在中期染色体双向定向的纠错机制中的作用。因此，UCHL3 有助于调节人类细胞中忠实的基因组分离和维持整倍性。表明其在中期染色体双向定向的纠错机制中的作用。因此，UCHL3 有助于调节人类细胞中忠实的基因组分离和维持整倍性。表明其在中期染色体双向定向的纠错机制中的作用。因此，UCHL3 有助于调节人类细胞中忠实的基因组分离和维持整倍性。