ArticleMolecular and cellular biology2012
Identification of a Src tyrosine kinase/SIAH2 E3 ubiquitin ligase pathway that regulates C/EBPδ expression and contributes to transformation of breast tumor cells.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 60 citations in OpenAlex.
- The autoimmune regulator (AIRE) is a target of the E3-Ubiquitin ligase Seven-in-absentia homolog 1 (SIAH1).Apoptosis : an international journal on programmed cell death · 2026Article
- Basic biology and roles of CEBPD in cardiovascular disease.Cell death discovery · 2025Review
- Tripartite motif containing 26 prevents steatohepatitis progression by suppressing C/EBPδ signalling activation.Nature communications · 2023Article
- Siah2-GRP78 interaction regulates ROS and provides a proliferative advantage to Helicobacter pylori-infected gastric epithelial cancer cells.Cellular and molecular life sciences : CMLS · 2022Article
- High-throughput formation and image-based analysis of basal-in mammary organoids in 384-well plates.Scientific reports · 2022Article
- CCAAT/Enhancer-Binding Proteins in Fibrosis: Complex Roles Beyond Conventional Understanding.Research (Washington, D.C.) · 2022Review
- Self-Sustained Regulation or Self-Perpetuating Dysregulation: ROS-dependent HIF-YAP-Notch Signaling as a Double-Edged Sword on Stem Cell Physiology and Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- PERK signaling through C/EBPδ contributes to ER stress-induced expression of immunomodulatory and tumor promoting chemokines by cancer cells.Cell death & disease · 2021Article
- Cell-Penetrating CEBPB and CEBPD Leucine Zipper Decoys as Broadly Acting Anti-Cancer Agents.Cancers · 2021Article
- Helicobacter pylori-induced gastric cancer is orchestrated by MRCKβ-mediated Siah2 phosphorylation.Journal of biomedical science · 2021Article
- Cancer Cell Invasion of Mammary Organoids with Basal-In Phenotype.Advanced healthcare materials · 2021Article
- Regulation of the SIAH2-HIF-1 Axis by Protein Kinases and Its Implication in Cancer Therapy.Frontiers in cell and developmental biology · 2021Review
- The "Janus" Role of C/EBPs Family Members in Cancer Progression.International journal of molecular sciences · 2020Review
- Article
- C/EBPδ protects from radiation-induced intestinal injury and sepsis by suppression of inflammatory and nitrosative stress.Scientific reports · 2019Article
- Identification and characterization of small molecule inhibitors of the ubiquitin ligases Siah1/2 in melanoma and prostate cancer cells.Cancer letters · 2019Article
- C/EBPδ links IL-6 and HIF-1 signaling to promote breast cancer stem cell-associated phenotypes.Oncogene · 2019Article
- Loss of C/EBPδ Exacerbates Radiation-Induced Cognitive Decline in Aged Mice due to Impaired Oxidative Stress Response.International journal of molecular sciences · 2019Article
- Regulation of Clock Genes by Adrenergic Receptor Signaling in Osteoblasts.Neurochemical research · 2018Review
- Bortezomib-induced miRNAs direct epigenetic silencing of locus genes and trigger apoptosis in leukemia.Cell death & disease · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
The transcription factor CCAAT/enhancer-binding protein delta (C/EBPδ, CEBPD) is a tumor suppressor that is downregulated during breast cancer progression but may also promote metastasis. Here, we have investigated the mechanism(s) regulating C/EBPδ expression and its role in human breast cancer cells. We describe a novel pathway by which the tyrosine kinase Src downregulates C/EBPδ through the SIAH2 E3 ubiquitin ligase. Src phosphorylates SIAH2 in vitro and leads to tyrosine phosphorylation and activation of SIAH2 in breast tumor cell lines. SIAH2 interacts with C/EBPδ, but not C/EBPβ, and promotes its polyubiquitination and proteasomal degradation. Src/SIAH2-mediated inhibition of C/EBPδ expression supports elevated cyclin D1 levels, phosphorylation of retinoblastoma protein (Rb), motility, invasive properties, and survival of transformed cells. Pharmacological inhibition of Src family kinases by SKI-606 (bosutinib) induces C/EBPδ expression in an SIAH2-dependent manner, which is necessary for "therapeutic" responses to SKI-606 in vitro. Ectopic expression of degradation-resistant mutants of C/EBPδ, which do not interact with SIAH2 and/or cannot be polyubiquitinated, prevents full transformation of MCF-10A cells by activated Src (Src truncated at amino acid 531 [Src-531]) in vitro. These data reveal that C/EBPδ expression can be regulated at the protein level by oncogenic Src kinase signals through SIAH2, thus contributing to breast epithelial cell transformation.
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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.