ArticleThe Journal of biological chemistry2013
Ubiquitination by the membrane-associated RING-CH-8 (MARCH-8) ligase controls steady-state cell surface expression of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptor 1.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 85 citations in OpenAlex.
- A pan-cancer analysis of MARCH8: molecular characteristics, clinical relevance, and immuno-oncology features.Cancer biology & therapy · 2025Article
- MARCH8 suppresses hepatocellular carcinoma by promoting SREBP1 degradation and modulating fatty acid de novo synthesis.Cell death & disease · 2025Article
- miR-335-5p Inhibits EMT and PI3K/AKT Pathways via MARCH8.Indian journal of clinical biochemistry : IJCB · 2025Article
- Role of MARCH E3 ubiquitin ligases in cancer development.Cancer metastasis reviews · 2024Review
- Article
- MARCH8 downregulation modulates profibrotic responses including myofibroblast differentiation.American journal of physiology. Cell physiology · 2023Article
- The emerging roles of MARCH8 in viral infections: A double-edged Sword.PLoS pathogens · 2023Review
- HPV upregulates MARCHF8 ubiquitin ligase and inhibits apoptosis by degrading the death receptors in head and neck cancer.PLoS pathogens · 2023Article
- Regulation of apoptosis by ubiquitination in liver cancer.American journal of cancer research · 2023Review
- Membrane-associated RING-CH protein (MARCH8) is a novel glycolysis repressor targeted by miR-32 in colorectal cancer.Journal of translational medicine · 2022Article
- Advances in HIV-1 Assembly.Viruses · 2022Review
- MARCH8 Targets Cytoplasmic Lysine Residues of Various Viral Envelope Glycoproteins.Microbiology spectrum · 2022Article
- Impact of Extracellular pH on Apoptotic and Non-Apoptotic TRAIL-Induced Signaling in Pancreatic Ductal Adenocarcinoma Cells.Frontiers in cell and developmental biology · 2022Article
- Rutaecarpine Increases Anticancer Drug Sensitivity in Drug-Resistant Cells through MARCH8-Dependent ABCB1 Degradation.Biomedicines · 2021Article
- MARCH8 inhibits influenza A virus infection by targeting viral M2 protein for ubiquitination-dependent degradation in lysosomes.Nature communications · 2021Article
- MARCH6 promotes hepatocellular carcinoma development through up-regulation of ATF2.BMC cancer · 2021Article
- MARCH8 Suppresses Tumor Metastasis and Mediates Degradation of STAT3 and CD44 in Breast Cancer Cells.Cancers · 2021Article
- Article
- When MARCH family proteins meet viral infections.Virology journal · 2021Review
- HSC70 Inhibits Spring Viremia of Carp Virus Replication by Inducing MARCH8-Mediated Lysosomal Degradation of G Protein.Frontiers in immunology · 2021Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The eleven members of the membrane-associated RING-CH (MARCH) ubiquitin ligase family are relatively unexplored. Upon exogenous (over)expression, a number of these ligases can affect the trafficking of membrane molecules. However, only for MARCH-1 endogenous functions have been demonstrated. For the other endogenous MARCH proteins, no functions or substrates are known. We report here that TRAIL-R1 is a physiological substrate of the endogenous MARCH-8 ligase. Human TRAIL-R1 and R2 play a role in immunosurveillance and are targets for cancer therapy, because they selectively induce apoptosis in tumor cells. We demonstrate that TRAIL-R1 is down-regulated from the cell surface, with great preference over TRAIL-R2, by exogenous expression of MARCH ligases that are implicated in endosomal trafficking, such as MARCH-1 and -8. MARCH-8 attenuated TRAIL-R1 cell surface expression and apoptosis signaling by virtue of its ligase activity. This suggested that ubiquitination of TRAIL-R1 was instrumental in its down-regulation by MARCH-8. Indeed, in cells with endogenous MARCH expression, TRAIL-R1 was ubiquitinated at steady-state, with the conserved membrane-proximal lysine 273 as one of the potential acceptor sites. This residue was also essential for the interaction of TRAIL-R1 with MARCH-1 and MARCH-8 and its down-regulation by these ligases. Gene silencing identified MARCH-8 as the endogenous ligase that ubiquitinates TRAIL-R1 and attenuates its cell surface expression. These findings reveal that endogenous MARCH-8 regulates the steady-state cell surface expression of TRAIL-R1.
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