ArticleScientific reports2014
USP8 modulates ubiquitination of LRIG1 for Met degradation.
Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Deciphering USP8's pivotal role in cancer: mechanisms, clinical insights and contrasts with its function in pituitary adenomas.Journal of translational medicine · 2025Review
- Article
- USP8 inhibitor-induced DNA damage activates cell cycle arrest, apoptosis, and autophagy in esophageal squamous cell carcinoma.Cell biology and toxicology · 2023Article
- Pharmaco-proteogenomic characterization of liver cancer organoids for precision oncology.Science translational medicine · 2023Article
- Ubiquitin-Specific Peptidase 8 Modulates Cell Proliferation and Induces Cell Cycle Arrest and Apoptosis in Breast Cancer by Stabilizing Estrogen Receptor Alpha.Journal of oncology · 2023Article
- Artonin F Induces the Ubiquitin-Proteasomal Degradation of c-Met and Decreases Akt-mTOR Signaling.Pharmaceuticals (Basel, Switzerland) · 2022Article
- USP8 regulates liver cancer progression via the inhibition of TRAF6-mediated signal for NF-κB activation and autophagy induction by TLR4.Translational oncology · 2022Article
- Paeoniflorin Inhibits EMT and Angiogenesis in Human GlioblastomaFrontiers in oncology · 2022Article
- Molecular basis of ubiquitin-specific protease 8 autoinhibition by the WW-like domain.Communications biology · 2021Article
- Ubiquitin-Specific Proteases: Players in Cancer Cellular Processes.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Destruction or Reconstruction: A Subtle Liaison between the Proteolytic and Signaling Role of Protein Ubiquitination in Spermatogenesis.Advances in experimental medicine and biology · 2021Article
- Depleting deubiquitinating enzymes promotes apoptosis in glioma cell line via RNA binding proteins SF2/ASF1.Biochemistry and biophysics reports · 2020Article
- Ubiquitin-specific protease 8 (USP8/UBPy): a prototypic multidomain deubiquitinating enzyme with pleiotropic functions.Biochemical Society transactions · 2019Review
- CHMP1B is a target of USP8/UBPY regulated by ubiquitin during endocytosis.PLoS genetics · 2018Article
- Review
- Article
- Novel strategy for a bispecific antibody: induction of dual target internalization and degradation.Oncogene · 2016Article
- The Endosome-associated Deubiquitinating Enzyme USP8 Regulates BACE1 Enzyme Ubiquitination and Degradation.The Journal of biological chemistry · 2016Article
- The LRIG family: enigmatic regulators of growth factor receptor signaling.Endocrine-related cancer · 2014Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Met receptor tyrosine kinase is an attractive target for cancer therapy as it promotes invasive tumor growth. SAIT301 is a novel anti-Met antibody, which induces LRIG1-mediated Met degradation and inhibits tumor growth. However, detailed downstream mechanism by which LRIG1 mediates target protein down-regulation is unknown. In the present study, we discovered that SAIT301 induces ubiquitination of LRIG1, which in turn promotes recruitment of Met and LRIG1 complex to the lysosome through its interaction with Hrs, resulting in concomitant degradation of both LRIG1 and Met. We also identified USP8 as a LRIG1-specific deubiquitinating enzyme, reporting the interaction between USP8 and LRIG1 for the first time. SAIT301 triggers degradation of LRIG1 by inhibiting the interaction of LRIG1 and USP8, which regulates ubiquitin modification and stability of LRIG1. In summary, SAIT301 employs ubiquitination of LRIG1 for its highly effective Met degradation. This unique feature of SAIT301 enables it to function as a fully antagonistic antibody without Met activation. We found that USP8 is involved in deubiquitination of LRIG1, influencing the efficiency of Met degradation. The relation of Met, LRIG1 and USP8 strongly supports the potential clinical benefit of a combination treatment of a USP8 inhibitor and a Met inhibitor, such as SAIT301.
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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.