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KIBRA Regulates Hippo Signaling Activity via Interactions with Large Tumor Suppressor Kinases
Open accessAbstract
The Hippo pathway controls tissue growth and tumorigenesis by inhibiting cell proliferation and promoting apoptosis. Recent genetic studies in Drosophila identified Kibra as a novel regulator of Hippo signaling. Human KIBRA has been associated with memory performance and cell migration. However, it is unclear whether or how KIBRA is connected to the Hippo pathway in mammalian cells. Here, we show that KIBRA associates with and activates Lats (large tumor suppressor) 1 and 2 kinases by stimulating their phosphorylation on the hydrophobic motif. KIBRA overexpression stimulates the phosphorylation of Yes-associated protein (YAP), the Hippo pathway effector. Conversely, depletion of KIBRA by RNA interference reduces YAP phosphorylation. Furthermore, KIBRA stabilizes Lats2 by inhibiting its ubiquitination. We also found that KIBRA mRNA is induced by YAP overexpression in both murine and human cells, suggesting the evolutionary conservation of KIBRA as a transcriptional target of the Hippo signaling pathway. Thus, our study revealed a new connection between KIBRA and mammalian Hippo signaling.
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“KIBRA can induce activation of LATS1/2 kinases and phosphorylation of the downstream effector YAP1 in the Hippo pathway (Xiao et al. 2011)”
From The Serine/Threonine Kinase NDR2 Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus (2025) · cites this paper as Xiao et al. 2011
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Metadata
- Authors
- Xiao, L., Chen, Y., Ji, M., & Dong, J.
- Affiliations
- University of Nebraska Medical Center (US)
- Corresponding author
- Ji, Ming
- Dong, Jixin
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 286
- Issue
- 10
- Pages
- 7788-7796
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3048666
- OpenAlex
- W2000662094
- Cited by
- 190
- References
- 47
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 7 · 2023: 12 · 2022: 13 · 2021: 14 · 2020: 12 · 2019: 11 · 2018: 14 · 2017: 17 · 2016: 11 · 2015: 14 · 2014: 13 · 2013: 19 · 2012: 11
- FWCI
- 7.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Health and Human Services
- University of Nebraska Medical Center
- Johns Hopkins University
- Nebraska Department of Health and Human Services
- National Institutes of Health
- National Center for Research Resources (5P20-RR018759-07, P20RR018759)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- KIBRA, Hippo signaling pathway, LATS1, LATS2, YAP, YAP phosphorylation, hydrophobic motif, kinase activation, ubiquitination, protein stability, transcriptional regulation, cell proliferation, apoptosis, tissue growth, carcinogenesis
- MeSH terms
- YAP-Signaling Proteins, Animals, Carrier Proteins, Drosophila melanogaster, Humans, Phosphoproteins, Phosphorylation, Proteins, Transcription Factors, Signal Transduction, Protein Serine-Threonine Kinases, Amino Acid Motifs, Tumor Suppressor Proteins, Cell Line, Tumor, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Mice, Ubiquitination, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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