ArticleOncotarget2017
Selective compounds enhance osteoblastic activity by targeting HECT domain of ubiquitin ligase Smurf1.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Ubiquitin-proteasome system regulation of bone remodeling in postmenopausal osteoporosis.Frontiers in cell and developmental biology · 2026Review
- Article
- The BMP Signaling Pathway: Bridging Maternal-Fetal Crosstalk in Early Pregnancy.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- SMURF1: a promising target for colon cancer therapy.Protein & cell · 2025Article
- NEDD4 family E3 ligases in osteoporosis: mechanisms and emerging potential therapeutic targets.Journal of orthopaedic surgery and research · 2025Review
- Targeting Smurf1 to block PDK1-Akt signaling in KRAS-mutated colorectal cancer.Nature chemical biology · 2025Article
- Hypoxia Promotes Osteoclast Differentiation by Weakening USP18-Mediated Suppression on the NF-κB Signaling Pathway.International journal of molecular sciences · 2024Article
- Role of ubiquitination in the occurrence and development of osteoporosis (Review).International journal of molecular medicine · 2024Review
- E3 ubiquitin ligases: key regulators of osteogenesis and potential therapeutic targets for bone disorders.Frontiers in cell and developmental biology · 2024Review
- Small-Molecule Probes as Pharmacological Tools for the Bone Morphogenetic Protein Signaling Pathway.ACS pharmacology & translational science · 2023Review
- The role of E3 ubiquitin ligases in bone homeostasis and related diseases.Acta pharmaceutica Sinica. B · 2023Review
- A cell-based high-throughput screening method based on a ubiquitin-reference technique for identifying modulators of E3 ligases.The Journal of biological chemistry · 2019Article
- Developing Small-Molecule Inhibitors of HECT-Type Ubiquitin Ligases for Therapeutic Applications: Challenges and Opportunities.Chembiochem : a European journal of chemical biology · 2018Review
- The Role of Smurf1 in Neuronal Necroptosis after Lipopolysaccharide-Induced Neuroinflammation.Cellular and molecular neurobiology · 2018Article
- ZC4H2 stabilizes Smads to enhance BMP signalling, which is involved in neural development inOpen biology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The HECT-type ubiquitin ligase Smurf1 (Smad ubiquitination regulatory factor-1) plays the prominent role in regulation of bone formation, embryonic development, and tumorigenesis by directing the ubiquitin-proteasomal degradation of specific targets. In contrast with RING-type E3s, the catalytic HECT domain of Smurf1 firstly binds to and then transfers ubiquitin (Ub) molecules onto the substrates. The Smurf1-Ub interaction is required for Smurf1 catalytic ligase activity to promote substrate degradation. However, so far specific regulators or compounds controlling Smurf1-Ub interaction and the ligase activity have not been identified. Here we report two small molecule compounds targeting Ub binding region of HECT domain interrupt Smurf1-Ub contact, inhibit Smurf1 ligase activity and stabilize BMP signal components Smad1/5 protein level. Furthermore, these compounds increase BMP signal responsiveness and enhance osteoblastic activity in cultured cells. These findings provide a novel strategy through targeting Smurf1 ligase activity to potentially treat bone disorders such as osteoporosis.
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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.