Cited by 15Hippo pathway signaling and YAP/TAZDevelopmental Biology and Gene RegulationMicrotubule and mitosis dynamics

Negative feedback couples Hippo pathway activation with Kibra degradation independent of Yorkie-mediated transcription

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Tokamov, Sherzod A, Su, Ting, Ullyot, Anne, Fehon, Richard G·2021·eLife

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Abstract

The Hippo (Hpo) pathway regulates tissue growth in many animals. Multiple upstream components promote Hpo pathway activity, but the organization of these different inputs, the degree of crosstalk between them, and whether they are regulated in a distinct manner is not well understood. Kibra (Kib) activates the Hpo pathway by recruiting the core Hpo kinase cassette to the apical cortex. Here, we show that the Hpo pathway downregulates Drosophila Kib levels independently of Yorkie-mediated transcription. We find that Hpo signaling complex formation promotes Kib degradation via SCF Slimb -mediated ubiquitination, that this effect requires Merlin, Salvador, Hpo, and Warts, and that this mechanism functions independently of other upstream Hpo pathway activators. Moreover, Kib degradation appears patterned by differences in mechanical tension across the wing. We propose that Kib degradation mediated by Hpo pathway components and regulated by cytoskeletal tension serves to control Kib-driven Hpo pathway activation and ensure optimally scaled and patterned tissue growth.

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  • β1 integrin signaling feeds back to the Hippo pathway, which can negatively regulate the expression of KIBRA.

    “β1 integrin signaling also feeds back to the Hippo pathway, which can negatively regulate the expression of KIBRA (Wong et al. 2016; Tokamov et al. 2021)”

    From The Serine/Threonine Kinase <scp>NDR2</scp> Regulates Integrin Signaling, Synapse Formation, and Synaptic Plasticity in the Hippocampus (2025) · cites this paper as Tokamov et al. 2021

    The Introduction states that the Hippo pathway lowers Kibra levels through post-translational degradation, supporting the negative-regulation part of the sentence. Our copy does not establish that β1 integrin signaling feeds back to the Hippo pathway, and its finding concerns Kibra protein abundance rather than transcriptional expression. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Tokamov, S. A., Su, T., Ullyot, A., & Fehon, R. G.
Affiliations
University of Chicago (US)
Corresponding author
Fehon, Richard G
Venue
eLife
Published
2021-02-08
Volume
10
ISSN
2050-084X (ISSN-L)
OpenAlex
W3127375543
Cited by
15
References
4
Citations by year
2026: 5 · 2025: 5 · 2023: 3 · 2022: 2
FWCI
0.65
Type
journal article
Language
en
Open access
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Knowledge@UChicago (University of Chicago) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • University of Chicago (cc-by)
Funders
  • National Institute of Neurological Disorders and Stroke (NS034783)
  • National Institute of General Medical Sciences (T32 GM007183)
  • National Science Foundation (Graduate Research Fellowship)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
Hippo signaling pathway, KIBRA, Yorkie, negative feedback, protein degradation, ubiquitination, Merlin, Salvador, Bahia, warts, mechanical tension, cytoskeletal tension, tissue growth regulation, Drosophila wing, signaling crosstalk
MeSH terms
Hippo Signaling Pathway, YAP-Signaling Proteins, Hippo Kinases, Animals, Drosophila melanogaster, Protein Binding, Protein Kinases, Transcription, Genetic, Protein Serine-Threonine Kinases, Tumor Suppressor Proteins, Neurofibromin 2, Drosophila Proteins, Intracellular Signaling Peptides and Proteins, Ubiquitination, Proteolysis

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