ArticleCell research2014
CKIP-1 regulates macrophage proliferation by inhibiting TRAF6-mediated Akt activation.
Article in Cell research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 75 citations in OpenAlex.
- Casein Kinase 2 Interacting Protein-1 Suppresses Glioma Cell Proliferation via Regulating the AKT/GSK3BioMed research international · 2019Trial
- Tissue-Resident Macrophage-Derived E3 Ligase SMURF2 Restricts Autoimmune Inflammation by Mediating the Degradation of p-TBK1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hsa-miR-194-5p regulates TRAF6-mediated M1 macrophage apoptosis in recurrent spontaneous abortion.Journal of molecular histology · 2025Article
- Breast milk induces the differentiation of monocytes into macrophages, promoting human cytomegalovirus infection.Journal of virology · 2024Article
- Regulation of Microglial Activation by Wnt/β-Catenin Signaling After Global Cerebral Ischemia in Mice.Molecular neurobiology · 2024Article
- Macrophage colony-stimulating factor and its role in the tumor microenvironment: novel therapeutic avenues and mechanistic insights.Frontiers in oncology · 2024Review
- IL-36α inhibits melanoma by inducing pro-inflammatory polarization of macrophages.Cancer immunology, immunotherapy : CII · 2023Article
- CKIP-1 mediatesJournal of oral microbiology · 2023Article
- Article
- Myeloid neddylation targets IRF7 and promotes host innate immunity against RNA viruses.PLoS pathogens · 2021Article
- Dysregulation of microRNA and Intracerebral Hemorrhage: Roles in Neuroinflammation.International journal of molecular sciences · 2021Review
- PLEKHO2 inhibits TNFα-induced cell death by suppressing RIPK1 activation.Cell death & disease · 2021Article
- Hepatocyte growth factor overexpression promotes osteoclastogenesis and exacerbates bone loss in CIA mice.Journal of orthopaedic translation · 2021Article
- Macrophage Function and the Role of GSK3.International journal of molecular sciences · 2021Review
- Macrophage NCOR1 Deficiency Ameliorates Myocardial Infarction and Neointimal Hyperplasia in Mice.Journal of the American Heart Association · 2020Article
- KDM4B facilitates colorectal cancer growth and glucose metabolism by stimulating TRAF6-mediated AKT activation.Journal of experimental & clinical cancer research : CR · 2020Article
- Super-enhancer-driven AJUBA is activated by TCF4 and involved in epithelial-mesenchymal transition in the progression of Hepatocellular Carcinoma.Theranostics · 2020Article
- Nanoscale Technologies for Prevention and Treatment of Heart Failure: Challenges and Opportunities.Chemical reviews · 2019Review
- NOTCH2 negatively regulates metastasis and epithelial-Mesenchymal transition via TRAF6/AKT in nasopharyngeal carcinoma.Journal of experimental & clinical cancer research : CR · 2019Article
- Sublytic C5b-9 induces proliferation of glomerular mesangial cells via ERK5/MZF1/RGC-32 axis activated by FBXO28-TRAF6 complex.Journal of cellular and molecular medicine · 2019Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophages play pivotal roles in development, homeostasis, tissue repair and immunity. Macrophage proliferation is promoted by macrophage colony-stimulating factor (M-CSF)-induced Akt signaling; yet, how this process is terminated remains unclear. Here, we identify casein kinase 2-interacting protein-1 (CKIP-1) as a novel inhibitor of macrophage proliferation. In resting macrophages, CKIP-1 was phosphorylated at Serine 342 by constitutively active GSK3β, the downstream target of Akt. This phosphorylation triggers the polyubiquitination and proteasomal degradation of CKIP-1. Upon M-CSF stimulation, Akt is activated by CSF-1R-PI3K and then inactivates GSK3β, leading to the stabilization of CKIP-1 and β-catenin proteins. β-catenin promotes the expression of proliferation genes including cyclin D and c-Myc. CKIP-1 interacts with TRAF6, a ubiquitin ligase required for K63-linked ubiquitination and plasma membrane recruitment of Akt, and terminates TRAF6-mediated Akt activation. By this means, CKIP-1 inhibits macrophage proliferation specifically at the late stage after M-CSF stimulation. Furthermore, CKIP-1 deficiency results in increased proliferation and decreased apoptosis of macrophages in vitro and CKIP-1(-/-) mice spontaneously develop a macrophage-dominated splenomegaly and myeloproliferation. Together, these data demonstrate that CKIP-1 plays a critical role in the regulation of macrophage homeostasis by inhibiting TRAF6-mediated Akt activation.
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