Department of Otolaryngology-Head and Neck Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Department of Nature Science, Center for General Studies, Chang Gung University, Taoyuan, Taiwan.
FEBS J. 2023 Dec;290(24):5704-5719. doi: 10.1111/febs.16926. Epub 2023 Aug 21.
YES-associated protein (YAP) is a part of the Hippo pathway, with pivotal roles in several developmental processes and dual functionality as both a tumor suppressor and an oncogene. In the present study, we identified YAP activity as a microtubular scaffold protein that maintains the stability of the mitotic spindle and midbody by physically interacting with α-tubulin during mitotic progression. The interaction of YAP and α-tubulin was evident in co-immunoprecipitation assays, as well as observing their co-localization in the microtubular structure of the mitotic spindle and midbody in immunostainings. With YAP depletion, levels of ECT2, MKLP-1, and Aurora B are reduced, which is consistent with YAP functioning in midbody formation during cytokinesis. The concomitant decrease in α-tubulin and increase in acetyl-α-tubulin during YAP depletion occurred at the post-transcriptional level. This suggests that YAP maintains the stability of the mitotic spindle and midbody, which ensures appropriate chromosome segregation during mitotic division. The increase in acetyl-α-tubulin during YAP depletion may provide a lesion-halting mechanism in maintaining the microtubule structure. The depletion of YAP also results in multinuclearity and aneuploidy, which supports its role in stabilizing the mitotic spindle and midbody.
Yes 相关蛋白（YAP）是 Hippo 信号通路的一部分，在多个发育过程中发挥关键作用，并且具有肿瘤抑制因子和癌基因的双重功能。在本研究中，我们发现 YAP 活性作为微管支架蛋白，通过在有丝分裂进程中与α-微管蛋白物理相互作用，维持着有丝分裂纺锤体和中体的稳定性。YAP 和α-微管蛋白的相互作用在共免疫沉淀实验中是明显的，并且在免疫染色中观察到它们在有丝分裂纺锤体和中体的微管结构中的共定位。随着 YAP 的耗竭，ECT2、MKLP-1 和 Aurora B 的水平降低，这与 YAP 在胞质分裂过程中参与中体形成的功能一致。YAP 耗竭时α-微管蛋白的同时减少和乙酰化α-微管蛋白的增加发生在转录后水平。这表明 YAP 维持着有丝分裂纺锤体和中体的稳定性，从而确保有丝分裂分裂过程中染色体的正确分离。YAP 耗竭时乙酰化α-微管蛋白的增加可能提供了一种在维持微管结构方面的损伤停止机制。YAP 的耗竭也导致多核和非整倍体，这支持了它在稳定有丝分裂纺锤体和中体方面的作用。
