ArticleCommunications biology2019
MEP50/PRMT5-mediated methylation activates GLI1 in Hedgehog signalling through inhibition of ubiquitination by the ITCH/NUMB complex.
Article in Communications biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 32 citations in OpenAlex.
- Protein arginine methylation and ubiquitination: A prominent crosstalk and its functions in cancer.Genes & diseases · 2026Review
- Bi-allelic PRMT9 loss-of-function variants cause a syndromic form of intellectual disability.American journal of human genetics · 2025Article
- Arginine methylation in cancer: mechanisms and therapeutic implications.Biomarker research · 2025Review
- Lysine and arginine methylation of transcription factors.Cellular and molecular life sciences : CMLS · 2024Review
- P4HA2 hydroxylates SUFU to regulate the paracrine Hedgehog signaling and promote B-cell lymphoma progression.Leukemia · 2024Article
- PRMT5-mediated methylation of STAT3 is required for lung cancer stem cell maintenance and tumour growth.Communications biology · 2024Article
- Review
- The HEDGEHOG-GLI1 pathway is important for fibroproliferative properties in keloids and as a candidate therapeutic target.Communications biology · 2023Article
- The Role of PRMT5 in Immuno-Oncology.Genes · 2023Review
- Protein arginine methylation in transcription and epigenetic regulation.Frontiers in epigenetics and epigenomics · 2023Review
- Statins Show Anti-Atherosclerotic Effects by Improving Endothelial Cell Function in a Kawasaki Disease-like Vasculitis Mouse Model.International journal of molecular sciences · 2022Article
- Multiprotein GLI Transcriptional Complexes as Therapeutic Targets in Cancer.Life (Basel, Switzerland) · 2022Review
- A Druggable UHRF1/DNMT1/GLI Complex Regulates Sonic Hedgehog-Dependent Tumor Growth.Molecular cancer research : MCR · 2022Article
- Article
- How Protein Methylation Regulates Steroid Receptor Function.Endocrine reviews · 2022Review
- Protein arginine methyltransferases: promising targets for cancer therapy.Experimental & molecular medicine · 2021Review
- Review
- PRMT5 in gene regulation and hematologic malignancies.Genes & diseases · 2019Review
- Non-canonical Hedgehog Signaling Pathway in Cancer: Activation of GLI Transcription Factors Beyond Smoothened.Frontiers in genetics · 2019Review
- Protein arginine methyltransferase 5 regulates SHH-subgroup medulloblastoma progression.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transcription factor GLI1 is an effecter of Hedgehog (HH) signalling and activated in a broad spectrum of cancers. However, the role of the HH-GLI1 pathway in cancer and the activation mechanism of GLI1 in HH signalling after dissociation from its inhibitor, SUFU, are not fully understood. Here, we found that GLI1 associated with the methylosome protein 50 (MEP50)/protein arginine methyltransferase 5 (PRMT5) complex and was methylated. Association of MEP50/PRMT5 with GLI1 was enhanced and expression of MEP50 and PRMT5 was activated by HH signals, suggesting their role in positive feedback regulation. Methylated GLI1 lost its ability to bind ubiquitin ligase ITCH/NUMB, resulting in nuclear accumulation and activation of GLI1. Moreover, protein expression of GLI1 was enhanced by MEP50/PRMT5 and expression of MEP50, PRMT5, and GLI1 target genes was upregulated in HH-expressing cancers. These results suggest that MEP50/PRMT5 is important for HH signal-induced GLI1 activation, especially in cancers.
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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 OpenQuestion graph.