Biomolecular condensates in Hippo pathway regulation

Yangqing SHAO; Yitong ZHANG; Wenxuan ZHU; Huasong LU

doi:10.1631/jzus.B2500092

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Reviews | Updated：2025-11-04

Biomolecular condensates in Hippo pathway regulation
Biomolecular condensates in Hippo pathway regulation
相分离凝聚体在Hippo信号通路中的调控作用
Journal of Zhejiang University-SCIENCE B Vol. 26, Issue 10, Pages: 949-960(2025)
Affiliations：

Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou 310058, China
Funds：
DOI：10.1631/jzus.B2500092
CLC：
CSTR：
Received：23 February 2025，

Revised：2025-04-10，

Published Online：22 September 2025，

Published：20 October 2025
Accepted：

邵阳晴,张怡童,朱文萱等.相分离凝聚体在Hippo信号通路中的调控作用[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(10):949-960.

Yangqing SHAO, Yitong ZHANG, Wenxuan ZHU, et al. Biomolecular condensates in Hippo pathway regulation[J]. Journal of zhejiang university-science b, 2025, 26(10): 949-960.
邵阳晴,张怡童,朱文萱等.相分离凝聚体在Hippo信号通路中的调控作用[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(10):949-960. DOI： 10.1631/jzus.B2500092.

Yangqing SHAO, Yitong ZHANG, Wenxuan ZHU, et al. Biomolecular condensates in Hippo pathway regulation[J]. Journal of zhejiang university-science b, 2025, 26(10): 949-960. DOI： 10.1631/jzus.B2500092.

摘要

Hippo信号通路作为一条高度保守的细胞信号转导途径，在细胞增殖和凋亡、器官大小发育以及组织再生等生物学过程中发挥着重要作用。该信号通路主要通过激酶级联反应，调控转录共激活因子YAP和TAZ的活性，进而影响下游靶基因表达。相关研究表明，YAP/TAZ在细胞核内可通过相分离机制形成凝聚体进而促进基因转录，但上述凝聚体的形成机制和动态调控过程尚不清楚。本文系统总结了相分离调控Hippo信号通路的最新研究进展，并重点介绍了YAP/TAZ凝聚体的转录调控功能。此外，本文还讨论了利用新型化学交联剂结合质谱技术解析TAZ凝聚体的互作网络，并发现FUS蛋白能够动态调控TAZ凝聚体的物质属性，即可通过维持其自身的液态流动性以促进TAZ的转录活性和促肿瘤发生的功能。相关研究的发现不仅加深了对Hippo信号通路调控机制的理解，也为YAP/TAZ活性失调相关疾病的靶向治疗提供了新的理论依据和潜在干预策略。

Abstract

Hippo signaling is a highly conserved pathway central to diverse cellular processes. Dysregulation of this pathway not only leads to developmental abnormalities but is also closely related to the occurrence and progression of various cancers. Recent studies have uncovered that

in addition to the classical signaling cascade regulation

biomolecular condensates formed via phase separation play a key role in the spatiotemporal regulation of Hippo signaling. In this review

we provide a summary of the latest research progress on the regulation of the Hippo signaling pathway by phase separation

with a particular focus on transcriptional activation mediated by Yes-associated protein (YAP)/transcriptional coactivator with post-synaptic density-95

disks-large

and zonula occludens-1 (PDZ)-binding domain (TAZ) condensates. Furthermore

we discuss the utility of chemical crosslinking combined with mass spectrometry to analyze the TAZ condensate interactome and examine the role of the protein fused in sarcoma (FUS) in modulating the biophysical properties of TAZ condensates

which in turn influence their transcriptional activity and pro-tumorigenic functions. These insights not only advance our understanding of Hippo signaling but also offer new perspectives for therapeutic interventions targeting diseases linked to dysregulated YAP/TAZ activity.

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references

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