ArticleProceedings of the National Academy of Sciences of the United States of America2016
E3 ubiquitin ligase RFWD2 controls lung branching through protein-level regulation of ETV transcription factors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 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, 38 citations in OpenAlex.
- Deubiquitination of ETV4 by USP7 Promotes NSCLC Tumorigenesis via MAPK7 Activation.Human mutation · 2026Article
- Ubiquitin-Activating Enzyme E1 (UBA1) as a Prognostic Biomarker and Therapeutic Target in Breast Cancer: Insights into Immune Infiltration and Functional Implications.International journal of molecular sciences · 2024Article
- ETV4 facilitates proliferation, migration, and invasion of liver cancer by mediating TGF-β signal transduction through activation of B3GNT3.Genes & genomics · 2023Article
- Article
- Spin column-based peptide fractionation alternatives for streamlined tandem mass tag (SL-TMT) sample processing.Journal of proteomics · 2023Article
- E26 transformation-specific transcription variant 5 in development and cancer: modification, regulation and function.Journal of biomedical science · 2023Review
- Lung epithelial cell-derived C3 protects against pneumonia-induced lung injury.Science immunology · 2023Article
- Preferential FGF18/FGFR activity in pseudoglandular versus canalicular stage human lung fibroblasts.Frontiers in cell and developmental biology · 2023Article
- Systematic prediction of degrons and E3 ubiquitin ligase binding via deep learning.BMC biology · 2022Article
- Ubiquitin ligases: guardians of mammalian development.Nature reviews. Molecular cell biology · 2022Review
- [Effects of ring finger and tryptophan-aspartic acid 2 on dendritic spines and synapse formation in cerebral cortex neurons of mice].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Stromal androgen and hedgehog signaling regulates stem cell niches in pubertal prostate development.Development (Cambridge, England) · 2021Article
- Discovery of key genes as novel biomarkers specifically associated with HPV-negative cervical cancer.Molecular therapy. Methods & clinical development · 2021Article
- Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development.International journal of molecular sciences · 2021Review
- Erk1/2 Inactivation-Induced c-Jun Degradation Is Regulated by Protein Phosphatases, UBE2d3, and the C-Terminus of c-Jun.International journal of molecular sciences · 2021Article
- Androgen action in cell fate and communication during prostate development at single-cell resolution.Development (Cambridge, England) · 2021Article
- Erk1/2 inactivation promotes a rapid redistribution of COP1 and degradation of COP1 substrates.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- E3 ubiquitin ligase MDM2 acts through p53 to control respiratory progenitor cell number and lung size.Development (Cambridge, England) · 2019Article
- Time-resolved proteome profiling of normal lung development.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Turing Instability-Driven Biofabrication of Branching Tissue Structures: A Dynamic Simulation and Analysis Based on the Reaction⁻Diffusion MechanismMicromachines · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The mammalian lung is an elaborate branching organ, and it forms following a highly stereotypical morphogenesis program. It is well established that precise control at the transcript level is a key genetic underpinning of lung branching. In comparison, little is known about how regulation at the protein level may play a role. Ring finger and WD domain 2 (RFWD2, also termed COP1) is an E3 ubiquitin ligase that modifies specific target proteins, priming their degradation via the ubiquitin proteasome system. RFWD2 is known to function in the adult in pathogenic processes such as tumorigenesis. Here, we show that prenatal inactivation of Rfwd2 gene in the lung epithelium led to a striking halt in branching morphogenesis shortly after secondary branch formation. This defect is accompanied by distalization of the lung epithelium while growth and cellular differentiation still occurred. In the mutant lung, two E26 transformation-specific (ETS) transcription factors essential for normal lung branching, ETS translocation variant 4 (ETV4) and ETV5, were up-regulated at the protein level, but not at the transcript level. Introduction of Etv loss-of-function alleles into the Rfwd2 mutant background attenuated the branching phenotype, suggesting that RFWD2 functions, at least in part, through degrading ETV proteins. Because a number of E3 ligases are known to target factors important for lung development, our findings provide a preview of protein-level regulatory network essential for lung branching morphogenesis.
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