严格控制中心体复制和分离对于防止染色体不稳定非常重要。中心粒的结构和数量变化是肿瘤细胞的标志性特征，并且有助于肿瘤发生。我们表明，中心粒扩增20（CA20）基因表达特征与三分子结构（TRIM）家族成员E3泛素连接酶TRIM69的高表达相关。在癌细胞中，TRIM69 去除导致中心体散布和染色体分离缺陷。我们识别了丝氨酸/苏氨酸蛋白激酶3（MST2）作为TRIM69的一种新的直接结合伴侣。TRIM69 重定位MST2到近核细胞骨架，促进其与极化样激酶1（PLK1）结合，并刺激MST2在S15位点（已知是中心粒分离的关键极化样激酶1磷酸化位点）的磷酸化。TRIM69还促进微管束缚和中心体分离，需要PRC1和DYNEIN。综上所述，我们确认TRIM69是调控中心体动态和促进二极分裂的新的近端调控因子。© 作者（们）2023年。由牛津大学出版社代表核酸研究发表。

Stringent control of centrosome duplication and separation is important for preventing chromosome instability. Structural and numerical alterations in centrosomes are hallmarks of neoplastic cells and contribute to tumorigenesis. We show that a Centrosome Amplification 20 (CA20) gene signature is associated with high expression of the Tripartite Motif (TRIM) family member E3 ubiquitin ligase, TRIM69. TRIM69-ablation in cancer cells leads to centrosome scattering and chromosome segregation defects. We identify Serine/threonine-protein kinase 3 (MST2) as a new direct binding partner of TRIM69. TRIM69 redistributes MST2 to the perinuclear cytoskeleton, promotes its association with Polo-like kinase 1 (PLK1) and stimulates MST2 phosphorylation at S15 (a known PLK1 phosphorylation site that is critical for centrosome disjunction). TRIM69 also promotes microtubule bundling and centrosome segregation that requires PRC1 and DYNEIN. Taken together, we identify TRIM69 as a new proximal regulator of distinct signaling pathways that regulate centrosome dynamics and promote bipolar mitosis.© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.