ArticleCell discovery2016
Dual function of partitioning-defective 3 in the regulation of YAP phosphorylation and activation.
Article in Cell discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Polarity dependent Hippo-Yap regulation controls cortical development.Research square · 2026Article
- aPKC-ζ III promotes trophoblast fusion by altering Par-3 interactions with Hippo signaling kinase LATS1.Stem cell reports · 2026Article
- PAR3-mediated coordination of hepatocyte proliferation, maturation, and architecture in liver development and regeneration.Nature communications · 2026Article
- Posttranslational modifications of YAP/TAZ: molecular mechanisms and therapeutic opportunities.Cellular & molecular biology letters · 2025Review
- The polarity protein Par3 enhances renal cell carcinoma metastasisCancer biology & medicine · 2025Article
- Par3/bazooka binds NICD and promotes notch signaling during Drosophila development.Developmental biology · 2024Article
- PARD3 drives tumorigenesis through activating Sonic Hedgehog signalling in tumour-initiating cells in liver cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- The Regulation of the Hippo Pathway by Intercellular Junction Proteins.Life (Basel, Switzerland) · 2022Review
- Dual Function of Par3 in Tumorigenesis.Frontiers in oncology · 2022Review
- Periodic Heat Stress Licenses EMSC Differentiation into Osteoblasts via YAP Signaling Pathway Activation.Stem cells international · 2022Article
- AMOTL2 mono-ubiquitination by WWP1 promotes contact inhibition by facilitating LATS activation.Life science alliance · 2021Article
- Inheritance and flexibility of cell polarity: a clue for understanding human brain development and evolution.Development (Cambridge, England) · 2021Article
- Host PDZ-containing proteins targeted by SARS-CoV-2.The FEBS journal · 2021Article
- The polarity protein PARD3 and cancer.Oncogene · 2021Review
- Endogenous YAP1 activation drives immediate onset of cervical carcinoma in situ in mice.Cancer science · 2020Article
- MAML1/2 promote YAP/TAZ nuclear localization and tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Tyrosine-Based Signals Regulate the Assembly of Daple⋅PARD3 Complex at Cell-Cell Junctions.iScience · 2020Article
- PAR3-PAR6-atypical PKC polarity complex proteins in neuronal polarization.Cellular and molecular life sciences : CMLS · 2018Review
- PARD3 dysfunction in conjunction with dynamic HIPPO signaling drives cortical enlargement with massive heterotopia.Genes & development · 2018Article
- Elevated expression of Par3 promotes prostate cancer metastasis by forming a Par3/aPKC/KIBRA complex and inactivating the hippo pathway.Journal of experimental & clinical cancer research : CR · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Partitioning-defective 3 (Par3), a key component of the evolutionarily conserved polarity PAR complex (Par3/Par6/aPKC), controls cell polarity and contributes to cell migration, proliferation and tumor development. Emerging evidence indicates that cell polarity proteins function as upstream modulators that regulate the Hippo pathway. However, little is known about Par3's involvement in the Hippo pathway. Here, we find Par3 and YAP dynamically co-localize in different subcellular compartments; that is, the membrane, cytoplasm and nucleus, in a cell-density-dependent manner. Interestingly, Par3 knockdown promotes YAP phosphorylation, leading to a significant impairment of YAP nuclear translocation at low cell density, but not at high density, in MDCK cells. Furthermore, via its third PDZ domain, Par3 directly binds to the PDZ-binding motif of YAP. The interaction is required for regulating YAP phosphorylation and nuclear localization. Mechanistically, Par3, as a scaffold protein, associates with LATS1 and protein phosphatase 1, α subunit (PP1A) in the cytoplasm and nucleus. Par3 promotes the dephosphorylation of LATS1 and YAP, thus enhancing YAP activation and cell proliferation. Strikingly, we also find that under the condition of PP1A knockdown, Par3 expression promotes YAP hyperphosphorylation, leading to the suppression of YAP activity and its downstream targets. Par3 expression results in differential effects on YAP phosphorylation and activation in different tumor cell lines. These findings indicate that Par3 may have a dual role in regulating the activation of the Hippo pathway, in a manner possibly dependent on cellular context or cell type in response to cell-cell contact and cell polarity signals.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.