ArticleOncotarget2018
The E3 ubiquitin ligase HERC1 controls the ERK signaling pathway targeting C-RAF for degradation.
Article in Oncotarget, 2018. 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, 39 citations in OpenAlex.
- Article
- Roles of E3 ubiquitin ligases and deubiquitinating enzymes in renal cell carcinoma.Frontiers in oncology · 2025Review
- The E3 ubiquitin ligase Herc1 modulates the response to nucleoside analogs in acute myeloid leukemia.Blood advances · 2024Article
- Insight into molecular basis and dynamics of full-length CRaf kinase in cellular signaling mechanisms.Biophysical journal · 2024Article
- MEK inhibitors: a promising targeted therapy for cardiovascular disease.Frontiers in cardiovascular medicine · 2024Review
- Investigation of Gene Networks in Three Components of Immune System Provides Novel Insights into Immune Response Mechanisms againstAnimals : an open access journal from MDPI · 2023Article
- Regulation of MAPK Signaling Pathways by the Large HERC Ubiquitin Ligases.International journal of molecular sciences · 2023Review
- HERC1 deficiency causes osteopenia through transcriptional program dysregulation during bone remodeling.Cell death & disease · 2023Article
- HERC2 deficiency activates C-RAF/MKK3/p38 signalling pathway altering the cellular response to oxidative stress.Cellular and molecular life sciences : CMLS · 2022Article
- Article
- A Novel ERK2 Degrader Z734 Induces Apoptosis of MCF-7 Cells via the HERC3/p53 Signaling Pathway.Molecules (Basel, Switzerland) · 2022Article
- Proteomic profiling of the oncogenic septin 9 reveals isoform-specific interactions in breast cancer cells.Proteomics · 2021Article
- Article
- RNA-Associated Co-expression Network Identifies Novel Biomarkers for Digestive System Cancer.Frontiers in genetics · 2021Article
- Dissecting the novel partners of nuclear c-Raf and its role in all-trans retinoic acid (ATRA)-induced myeloblastic leukemia cells differentiation.Experimental cell research · 2020Article
- The non-linearity of RAF-MEK signaling in dendritic cells.Cell cycle (Georgetown, Tex.) · 2020Review
- The HERC1 ubiquitin ligase regulates presynaptic membrane dynamics of central synapses.Scientific reports · 2020Article
- HERC Ubiquitin Ligases in Cancer.Cancers · 2020Review
- Immune correlates of tuberculosis disease and risk translate across species.Science translational medicine · 2020Article
- HERC1 Ubiquitin Ligase Is Required for Hippocampal Learning and Memory.Frontiers in neuroanatomy · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The RAF/MEK/ERK cascade is a conserved intracellular signaling pathway that controls fundamental cellular processes including growth, proliferation, differentiation, survival and migration. Aberrant regulation of this signaling pathway has long been associated with human cancers. A major point of regulation of this pathway occurs at the level of the serine/threonine protein kinase C-RAF. Here, we show how the E3 ubiquitin ligase HERC1 regulates ERK signaling. HERC1 knockdown induced cellular proliferation, which is associated with an increase in ERK phosphorylation and in C-RAF protein levels. We demonstrate that overexpression of wild-type C-RAF is sufficient to increase ERK phosphorylation. Experiments with pharmacological inhibitors of RAF activity, or with interference RNA, show that the regulation of ERK phosphorylation by HERC1 is RAF-dependent. Immunoprecipitation, pull-down and confocal fluorescence microscopy experiments demonstrate an interaction between HERC1 and C-RAF proteins. Mechanistically, HERC1 controls C-RAF stability by regulating its polyubiquitylation in a lysine 48-linked chain.
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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.