Thymic CD4 T cell selection requires attenuation of March8-mediated MHCII turnover in cortical epithelial cells through CD83

Rohrscheidt, Julia von; Petrozziello, Elisabetta; Nedjic, Jelena; Federle, Christine; Krzyzak, Lena; Ploegh, Hidde L.; Ishido, Satoshi; Steinkasserer, Alexander; Klein, Ludger

doi:10.1084/jem.20160316

Cited by 67 publications

(82 citation statements)

References 30 publications

(50 reference statements)

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“…[25][26][27][28][29] Ubiquitin has an ability to control membrane protein expression and localization and exert significant influence on cellular function. Specifically, MARCH1 was shown to be capable of ubiquitinating MHCII and mediating intracellular localization and lysosomal degradation of MHC II in DCs and B cells.…”

Section: Discussionmentioning

confidence: 99%

MARCH1 encourages tumour progression of hepatocellular carcinoma via regulation of PI3K‐AKT‐β‐catenin pathways

Xie

Dai

et al. 2019

J Cellular Molecular Medi

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Membrane‐associated RING‐CH‐1 (MARCH1) is a membrane‐anchored E3 ubiquitin ligase that is involved in a variety of cellular processes. MARCH1 was aberrantly expressed as a tumour promoter in ovarian cancer, but the signalling about the molecular mechanism has not yet been fully illuminated. Here, we first determined that MARCH1 was obviously highly expressed in human hepatocellular carcinoma samples and cells. In addition, our findings demonstrated that the proliferation, migration and invasion of hepatocellular carcinoma were suppressed, but the apoptosis was increased, as a result of MARCH1 knockdown by either siRNA targeting MARCH1 or pirarubicin treatment. Conversely, the proliferation, migration and invasion of hepatocellular carcinoma were obviously accelerated, and the apoptosis was decreased, by transfecting the MARCH1 plasmid to make MARCH1 overexpressed. Moreover, in vivo, the results exhibited a significant inhibition of the growth of hepatocellular carcinoma in nude mice, which were given an intra‐tumour injection of siRNA targeting MARCH1. Furthermore, our study concluded that MARCH1 functions as a tumour promoter, and its role was up‐regulated the PI3K‐AKT‐β‐catenin pathways both in vitro and in vivo. In summary, our work determined that MARCH1 has an important role in the development and progression of hepatocellular carcinoma and may be used as a novel potential molecular therapeutic target in the future treatment of hepatocellular carcinoma.

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Section: Discussionmentioning

confidence: 99%

MARCH1 encourages tumour progression of hepatocellular carcinoma via regulation of PI3K‐AKT‐β‐catenin pathways

Xie

Dai

et al. 2019

J Cellular Molecular Medi

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“…70, 71 CD83 regulates B cell activation and germinal center responses 72 as well as CD4 + T cell development. 73, 74 Although largely expressed by activated APCs, the costimulatory function of CD83 seems to be dispensable for murine T cell activation whilst CD83-stimulated human monocytes suppressed T cell responses. 75, 76 However, the role and function of CD83 in cardiovascular disease is so far unidentified.…”

Section: Co-stimulatory Pathways In Atherosclerosismentioning

confidence: 99%

ATVB Distinguished Scientist Award

Ley

Gerdes

Winkels

2017

ATVB

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Objective Immune cells play a critical role in atherosclerosis. Co-stimulatory and co-inhibitory molecules of the tumor necrosis factor receptor and CD28 immunoglobulin superfamilies shape T cell and B cell responses, but also have a major effect on antigen presenting cells and non-immune cells. Approach and Results Pharmacological inhibition or activation of co-stimulatory and co-inhibitory molecules as well as genetic deletion demonstrated their involvement in atherosclerosis. This review highlights recent advances in understanding how co-stimulatory and co-inhibitory pathways shape the immune response in atherosclerosis. Conclusion Insights gained from co-stimulatory and co-inhibitory molecule function in atherosclerosis may inform future therapeutic approaches.

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“…MARCH8(also called c‐MIR and RNF178), a member of the newly discovered MARCH family of (RING) E3 ligases, has been reported to downregulate numerous proteins including major histocompatibility complex (MHC)‐II, CD86, interleukin (IL)‐1 receptor accessory protein, TNF‐related apoptosis‐inducing ligand (TRAIL) receptor 1 and the transferrin receptor (Chen et al, ; Bayer‐Santos et al, ; Sun et al, ; von Rohrscheidt et al, ). The functions of MARCH8 have been mostly studied in immune cells, and MARCH8 has been reported to be dysregulated in human cancers including lung cancer (Fan et al, ) and gastric cancer (Yin et al, ).…”

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confidence: 99%

The E3 Ubiquitin Ligase MARCH8 Regulates TNF‐α‐Induced Apoptosis in Hippocampal Neurons by Targeting Myosin Light Chain 2 for Degradation

Guo

Zhang

Wei

et al. 2019

The Anatomical Record

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Tumor necrosis factor‐α (TNF‐α) is an important inflammatory cytokine that plays a key role in neuronal damage. Elevated expression of TNF‐α is associated with numerous neurodegenerative diseases including Alzheimer's Disease and Parkinson's Disease. However, the specific mechanism of the signaling events that trigger TNF‐α‐mediated neurotoxicity remain unknown. In this study, we report that intracerebroventricular injection of TNF‐α in rat hippocampal neurons down‐regulates MLC2 and up‐regulates MARCH8, an essential light chain and regulatory myosin light chain of NM Myosin II, respectively. MARCH8 overexpression attenuates the degradation of MLC2 by promoting its ubiquitination and degradation. Inhibition of MARCH8 by siRNA blocks caspase‐3 activation and apoptosis signaling, suggesting that TNF‐α‐induced apoptosis of neurons is partially dependent on the accumulation of MARCH8 and the ubiquitination of MLC2. Taken together, our data not only clarify the function of MARCH8 in TNF‐α‐induced neurotoxicity, but also demonstrates that TNF‐α promotes the MARCH8‐MLC2 mediated apoptosis of hippocampal neurons. Anat Rec, 302:2271–2278, 2019. © 2019 American Association for Anatomy

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Thymic CD4 T cell selection requires attenuation of March8-mediated MHCII turnover in cortical epithelial cells through CD83

Abstract: Work from the Klein lab shows that CD83 supports T cell selection in the thymus by restraining March8-mediated MHCII ubiquitination and internalization.

Cited by 67 publications

References 30 publications

MARCH1 encourages tumour progression of hepatocellular carcinoma via regulation of PI3K‐AKT‐β‐catenin pathways

MARCH1 encourages tumour progression of hepatocellular carcinoma via regulation of PI3K‐AKT‐β‐catenin pathways

ATVB Distinguished Scientist Award

The E3 Ubiquitin Ligase MARCH8 Regulates TNF‐α‐Induced Apoptosis in Hippocampal Neurons by Targeting Myosin Light Chain 2 for Degradation

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