ArticleNature communications2023
A ubiquitin-based effector-to-inhibitor switch coordinates early brain, craniofacial, and skin development.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- TP53 drives neuronal ferroptosis by promoting KLHL4-mediated SLC7A11 ubiquitination after spinal cord injury.Neural regeneration research · 2026Article
- Decoding unchanged transcriptome of Alzheimer's disease reveals an NCAM1 mRNA switch as a potential biomarker.iScience · 2026Article
- KLHL4 upregulates EGFR signaling to promote the malignant progression of oral squamous cell carcinoma.Medical oncology (Northwood, London, England) · 2025Article
- The E3 ubiquitin ligase adaptor KLHL8 targets ZAR1 to regulate maternal mRNA degradation in oocytes.EMBO reports · 2025Article
- Zebrafish Kelch-like family member 4 is required for vasculogenesis and hematopoiesis.Developmental biology · 2025Article
- KLHL23 and RhoGDI coordinate CDC42 inactivation ensuring membrane homeostasis.Nature chemical biology · 2025Article
- Neuroplasticity and Nervous System Recovery: Cellular Mechanisms, Therapeutic Advances, and Future Prospects.Brain sciences · 2025Review
- [Study on the correlation between high expression of GIT1 and M2 macrophage infiltration and prognosis in hepatocellular carcinoma].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Article
- You can "tail" them apart: paralog-specific functions of CRL4B ubiquitin ligases during mitosis and brain development.The EMBO journal · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
The molecular mechanisms that coordinate patterning of the embryonic ectoderm into spatially distinct lineages to form the nervous system, epidermis, and neural crest-derived craniofacial structures are unclear. Here, biochemical disease-variant profiling reveals a posttranslational pathway that drives early ectodermal differentiation in the vertebrate head. The anteriorly expressed ubiquitin ligase CRL3-KLHL4 restricts signaling of the ubiquitous cytoskeletal regulator CDC42. This regulation relies on the CDC42-activating complex GIT1-βPIX, which CRL3-KLHL4 exploits as a substrate-specific co-adaptor to recognize and monoubiquitylate PAK1. Surprisingly, we find that ubiquitylation converts the canonical CDC42 effector PAK1 into a CDC42 inhibitor. Loss of CRL3-KLHL4 or a disease-associated KLHL4 variant reduce PAK1 ubiquitylation causing overactivation of CDC42 signaling and defective ectodermal patterning and neurulation. Thus, tissue-specific restriction of CDC42 signaling by a ubiquitin-based effector-to-inhibitor is essential for early face, brain, and skin formation, revealing how cell-fate and morphometric changes are coordinated to ensure faithful organ development.
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Registered trials
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 Socratic graph.