ArticleMolecular and cellular biology2014
HUWE1 is a molecular link controlling RAF-1 activity supported by the Shoc2 scaffold.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- The expression of congenital Shoc2 variants induces AKT-dependent crosstalk activation of the ERK1/2 pathway.Human molecular genetics · 2024Article
- RAS and SHOC2 Roles in RAF Activation and Therapeutic Considerations.Annual review of cancer biology · 2024Article
- SHOC2 plays an oncogenic or tumor-suppressive role by differentially targeting the MAPK and mTORC1 signals in liver cancer.Life medicine · 2024Article
- Deciphering the crystal structure of a novel nanobody against the NEIL1 DNA glycosylase.Acta crystallographica. Section D, Structural biology · 2024Article
- HUWE1 controls tristetraprolin proteasomal degradation by regulating its phosphorylation.eLife · 2023Article
- Regulation of MAPK Signaling Pathways by the Large HERC Ubiquitin Ligases.International journal of molecular sciences · 2023Review
- Shoc2 controls ERK1/2-driven neural crest development by balancing components of the extracellular matrix.Developmental biology · 2022Article
- USP7 regulates the ERK1/2 signaling pathway through deubiquitinating Raf-1 in lung adenocarcinoma.Cell death & disease · 2022Article
- Involvement of HECT-type E3 ubiquitin ligase genes in salt chemotaxis learning in Caenorhabditis elegans.Genetics · 2022Article
- Shoc2 recognizes bacterial flagellin and mediates antibacterial Erk/Stat signaling in an invertebrate.PLoS pathogens · 2022Article
- The role of USP7 in the Shoc2-ERK1/2 signaling axis and Noonan-like syndrome with loose anagen hair.Journal of cell science · 2021Article
- Kinase-Catalyzed Biotinylation to Map Cell Signaling Pathways: Application to Epidermal Growth Factor Signaling.Journal of proteome research · 2021Article
- A Leucine-Rich Repeat Protein Provides a SHOC2 the RAS Circuit: a Structure-Function Perspective.Molecular and cellular biology · 2021Review
- The leucine-rich repeat signaling scaffolds Shoc2 and Erbin: cellular mechanism and role in disease.The FEBS journal · 2021Review
- SHOC2 scaffold protein modulates daunorubicin-induced cell death through p53 modulation in lymphoid leukemia cells.Scientific reports · 2020Article
- The E3 ligase HUWE1 inhibition as a therapeutic strategy to target MYC in multiple myeloma.Oncogene · 2020Article
- Single-domain antibodies for functional targeting of the signaling scaffold Shoc2.Molecular immunology · 2020Article
- SHOC2 complex-driven RAF dimerization selectively contributes to ERK pathway dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- VCP/p97 controls signals of the ERK1/2 pathway transmitted via the Shoc2 scaffolding complex: novel insights into IBMPFD pathology.Molecular biology of the cell · 2019Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Scaffold proteins play a critical role in controlling the activity of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. Shoc2 is a leucine-rich repeat scaffold protein that acts as a positive modulator of ERK1/2 signaling. However, the precise mechanism by which Shoc2 modulates the activity of the ERK1/2 pathway is unclear. Here we report the identification of the E3 ubiquitin ligase HUWE1 as a binding partner and regulator of Shoc2 function. HUWE1 mediates ubiquitination and, consequently, the levels of Shoc2. Additionally, we show that both Shoc2 and HUWE1 are necessary to control the levels and ubiquitination of the Shoc2 signaling partner, RAF-1. Depletion of HUWE1 abolishes RAF-1 ubiquitination, with corresponding changes in ERK1/2 pathway activity occurring. Our results indicate that the HUWE1-mediated ubiquitination of Shoc2 is the switch that regulates the transition from an active to an inactive state of the RAF-1 kinase. Taken together, our results demonstrate that HUWE1 is a novel player involved in regulating ERK1/2 signal transmission through the Shoc2 scaffold complex.
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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.