ArticleCell death and differentiation2014
Ubiquitination by SAG regulates macrophage survival/death and immune response during infection.
Article in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Siah2 regulates lipid uptake in adipose tissue macrophages.The Journal of biological chemistry · 2026Article
- PD-1/PD-L1 Cancer Immunotherapeutics Reshape Tumor Microenvironment - Clinical Evidence and Molecular Mechanisms for AI-based Precision Medicine.Clinical reviews in allergy & immunology · 2025Review
- The Ubiquitin-Proteasome System: A Key Regulatory Hub in Myocarditis Leading to Dilated Cardiomyopathy.Journal of inflammation research · 2025Review
- Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.Molecular cancer · 2024Review
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Ubiquitin Signaling in the Immune System.Advances in experimental medicine and biology · 2024Review
- RNF7 Induces Skeletal Muscle Cell Apoptosis and Arrests Cell Autophagy via Upregulation of THBS1 and Inactivation of the PI3K/Akt Signaling Pathway in a Rat Sepsis Model.Infection and immunity · 2023Article
- Roles of ubiquitination in the crosstalk between tumors and the tumor microenvironment (Review).International journal of oncology · 2022Review
- A Novel Signature of CCNF-Associated E3 Ligases Collaborate and Counter Each Other in Breast Cancer.Cancers · 2021Article
- Neddylation Regulates Macrophages and Implications for Cancer Therapy.Frontiers in cell and developmental biology · 2021Review
- Article
- Neddylation: A Versatile Pathway Takes on Chronic Liver Diseases.Frontiers in medicine · 2020Review
- Neddylation: a novel modulator of the tumor microenvironment.Molecular cancer · 2019Review
- Protein neddylation and its alterations in human cancers for targeted therapy.Cellular signalling · 2018Review
- SAG/RBX2 E3 Ubiquitin Ligase Differentially Regulates Inflammatory Responses of Myeloid Cell Subsets.Frontiers in immunology · 2018Article
- β-Defensins in the Fight against Helicobacter pylori.Molecules (Basel, Switzerland) · 2017Review
- Reduced Expression of SARM in Mouse Spleen during Polymicrobial Sepsis.Inflammation · 2016Article
- Mycobacterium avium MAV2054 protein induces macrophage apoptosis by targeting mitochondria and reduces intracellular bacterial growth.Scientific reports · 2016Article
- SAG-UPS regulates malignant transformation--from chronic inflammation to pro-tumorigenesis to liver cancer.Cell death & disease · 2015Article
- SAG-UPS attenuates proapoptotic SARM and Noxa to confer survival advantage to early hepatocellular carcinoma.Cell death discovery · 2015Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The checkpoint between the life and death of macrophages is crucial for the host's frontline immune defense during acute phase infection. However, the mechanism as to how the immune cell equilibrates between apoptosis and immune response is unclear. Using in vitro and ex vivo approaches, we showed that macrophage survival is synchronized by SAG (sensitive to apoptosis gene), which is a key member of the ubiquitin-proteasome system (UPS). When challenged by pathogen-associated molecular patterns (PAMPs), we observed a reciprocal expression profile of pro- and antiapoptotic factors in macrophages. However, SAG knockdown disrupted this balance. Further analysis revealed that ubiquitination of Bax and SARM (sterile α- and HEAT/armadillo-motif-containing protein) by SAG-UPS confers survival advantage to infected macrophages. SAG knockdown caused the accumulation of proapoptotic Bax and SARM, imbalance of Bcl-2/Bax in the mitochondria, induction of cytosolic cytochrome c and activation of caspase-9 and -3, all of which led to disequilibrium between life and death of macrophages. In contrast, SAG-overexpressing macrophages challenged with PAMPs exhibited upregulation of protumorigenic cytokines (IL-1β, IL-6 and TNF-α), and downregulation of antitumorigenic cytokine (IL-12p40) and anti-inflammatory cytokine (IL-10). This suggests that SAG-dependent UPS is a key switch between immune defense and apoptosis or immune overactivation and tumorigenesis. Altogether, our results indicate that SAG-UPS facilitates a timely and appropriate level of immune response, prompting future development of potential immunomodulators of SAG-UPS.
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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.