AMFR

Alveolar macrophages (AMs) are specialized tissue-resident macrophages that orchestrate the immune response in allergic inflammation and asthma. However, what signals direct AMs to cross talk with other immune cells remains unclear. Here, we report that autocrine motility factor receptor (AMFR), an endoplasmic reticulum-resident E3 ubiquitin ligase, is upregulated in AMs of asthma and is critical for this condition. AMFR deficiency significantly decreased allergy-induced T helper 2 (Th2) and eosinophilic inflammation, with less granulocyte-macrophage colony-stimulating factor (GM-CSF) production in AMs...

Contents of milk fatty acids (FA) display remarkable alterations along climatic gradients. Detecting candidate genes underlying such alterations might be beneficial for the exploration of climate sensitivity in dairy cattle. Consequently, we aimed on the definition of FA heat stress indicators, considering FA breeding values in response to temperature-humidity index (THI) alterations. Indicators were used in GWAS, in ongoing gene annotations and for the estimation of chromosome-wide variance components. The phenotypic data set consisted of 39,600 test-day milk FA records from 5,757 first-lactation Holstein dairy cows kept in 16 large-scale German cooperator herds...

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BACKGROUND: Sarcopenic obesity aims to capture the risk of functional decline and cardiometabolic diseases, but its operational definition and associated clinical outcomes remain unclear. Using data from the Longitudinal Aging Study of Taipei, this study explored the roles of the muscle-to-fat ratio (MFR) with different definitions and its associations with clinical characteristics, functional performance, cardiometabolic risk and outcomes. METHODS: (1) Appendicular muscle mass divided by total body fat mass (aMFR), (2) total body muscle mass divided by total body fat mass (tMFR) and (3) relative appendicular skeletal muscle mass (RASM) were measured...

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Regulation of the mammalian embryo involves cell-signaling molecules produced by the maternal oviduct and endometrium. Here, datasets on the transcriptome of the gestational Days 5 and 6 bovine morula and Day 5 maternal endometrium were examined to identify receptor genes expressed by the morula and expression of the corresponding ligand-related genes in the endometrium. A total of 175 receptor genes were identified in the morula, including 48 encoding for growth factors or WNT signaling molecules, 25 for cytokines and chemokines, 35 involved in juxtacrine and matricellular signaling and 25 encoding for receptors for small molecules...

Recruitment of immune cells to the site of inflammation by the chemokine CCL1 is important in the pathology of inflammatory diseases. Here, we examined the role of CCL1 in pulmonary fibrosis (PF). Bronchoalveolar lavage fluid from PF mouse models contained high amounts of CCL1, as did lung biopsies from PF patients. Immunofluorescence analyses revealed that alveolar macrophages and CD4+ T cells were major producers of CCL1 and targeted deletion of Ccl1 in these cells blunted pathology. Deletion of the CCL1 receptor Ccr8 in fibroblasts limited migration, but not activation, in response to CCL1...

WNT signalling is important for development in all metazoans and is associated with various human diseases. The ubiquitin-proteasome system (UPS) and regulatory endoplasmic reticulum-associated degradation (ERAD) have been implicated in the production of WNT proteins. Here, we investigated how the WNT secretory factor EVI (also known as WLS) is ubiquitylated, recognised by ERAD components and subsequently removed from the secretory pathway. We performed a focused immunoblot-based RNAi screen for factors that influence EVI/WLS protein stability...

WNT signalling is important for development in all metazoan animals and is associated with various human diseases. The Ubiquitin-Proteasome System (UPS) and regulatory ER-associated degradation (ERAD) have been implicated in the production of WNT proteins. Here, we investigated how the WNT secretory factor EVI/WLS is ubiquitinated, recognised by ERAD components and subsequently removed from the secretory pathway. We performed a focused, immunoblot-based RNAi screen for factors that influence EVI/WLS protein stability...

Human hepatic tryptophan 2,3-dioxygenase (hTDO) is a homotetrameric hemoprotein. It is one of the most rapidly degraded liver proteins with a half-life (t1/2) of ~2.3 h, relative to an average t1/2 of ~2-3 days for total liver protein. The molecular mechanism underlying the poor longevity of hTDO remains elusive. Previously, we showed that hTDO could be recognized and ubiquitinated by two E3 ubiquitin (Ub) ligases, gp78/AMFR and CHIP, and subsequently degraded via Ub-dependent proteasomal degradation (UPD) pathway...

Autocrine motility factor (AMF) stimulates the motility of cancer cells via an autocrine route and has been implicated in tumor progression and metastasis. Overexpression of AMF is correlated with the aggressive nature of breast cancer and is negatively associated with clinical outcomes. In contrast, AMF also has the ability to suppress cancer cells. In this study, AMFs from different cancer cells were demonstrated to have suppressive activity against MCF-7 and MDA-MB-231 breast cancer cells. In a growth and colony formation assay, AMF from AsPC-1 pancreatic cancer cells (ASPC-1:AMF) was determined to be more suppressive compared to other AMFs...

The conserved zona pellucida (ZP) domain is found in hundreds of extracellular proteins that are expressed in various organs and play a variety of roles as structural components, receptors and tumor suppressors. A liver-specific zona pellucida domain-containing protein (LZP), also named OIT3, has been shown to be mainly expressed in human and mouse hepatocytes; however, the physiological function of LZP in the liver remains unclear. Here, we show that Lzp deletion inhibited very low-density lipoprotein (VLDL) secretion, leading to hepatic TG accumulation and lower serum TG levels in mice...

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Epilepsy can severely affect the quality of life of patients, who are often at higher risk of mortality. However, the molecular mechanisms and pathogenesis underlying epileptogenesis are poor understood. In this study, we performed a proteomic analysis of the hippocampus in pentylenetetrazole (PTZ)-kindled epileptic rats to explore the molecular mechanisms of epileptogenesis. We established an epileptic model in Sprague-Dawley rats by injecting PTZ intraperitoneally and applied isobaric tags for relative and absolute quantification (iTRAQ) technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins (DEPs) in the hippocampus...

Hepatic cytochrome P450 CYP2E1 is an enzyme engaged in the metabolic biotransformation of various xenobiotics and endobiotics, resulting in both detoxification and/or metabolic activation of its substrates to more therapeutic or toxic products. Elevated hepatic CYP2E1 content is implicated in various metabolic diseases including alcoholic liver disease, nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), diabetes and obesity. While hepatic CYP2E1 elevation is considered essential to the pathogenesis of these liver diseases, our findings in two mouse models of E3 ubiquitin ligase genetic ablation fed a regular lab chow diet, argue that it is not sufficient for triggering NAFLD/NASH...

AMFR/gp78 and USP13 are a pair of ubiquitin ligase and deubiquitinase that ensure the accuracy of endoplasmic reticulum-associated degradation (ERAD). Depletion of USP13 leads to caspase activation and cleavage of the ERAD chaperone BAG6, which is reversed by knockdown of AMFR . However, the mechanism and physiological relevance of this regulation are still unclear. Here, by using the NEDDylator system, we screened out TXN as a substrate of AMFR and USP13 and showed its involvement in regulating CASP3 activation and BAG6 cleavage...

Management of aggressive malignant musculoskeletal tumors is clinically challenging and awaits the identification of regulator(s) that can be therapeutically used to improve patient outcome. Autocrine motility factor (AMF), a secreted cytokine, is known to alter the bone microenvironment by linking to its receptor AMFR (AMF Receptor), leading to tumor progression. It was noted that both the ligand and its receptor belong to the moonlighting family of proteins, as they contribute to intracellular metabolic function such as glycolysis and gluconeogenesis by expressing glucose-6-phosphate isomerase AMF/GPI and higher protein degradation by expressing AMFR/gp78 functioning as ubiquitin ligase activity...

Despite widespread utilization of immunotherapy, treating immune-cold tumors has proved to be a challenge. Here, we report that expression of the immune checkpoint molecule B7-H4 is prevalent among immune-cold triple-negative breast cancers (TNBC), where its expression inversely correlates with that of PD-L1. Glycosylation of B7-H4 interferes with its interaction/ubiquitination by AMFR, resulting in B7-H4 stabilization. B7-H4 expression inhibits doxorubicin-induced cell death through the suppression of eIF2α phosphorylation required for calreticulin exposure vis-à-vis the cancer cells...

Autocrine motility factor (AMF: GPI) and its receptor AMFR (AMF Receptor: gp78) regulate the metastatic process. Here, we have tested the expression levels of AMF, AMFR, and AMF × AMFR in 1348 patients with musculoskeletal tumor. The results depicted here identified that multiple myeloma highly express AMF × AMFR value as compared with normal bone samples (p < 0.00001). To visualize the AMF × AMFR autocrine amplification in multiple myeloma microenvironment, we have developed a novel software aimed at analyzing numerous cell-to-cell and ligand-to-receptor interactions, i...

Larimichthys polyactis is a commercially important marine fish species in Eastern Asia, yet very few genetic resources exist. In particular, genetic linkage maps are critical tools for genetic breeding. In this study, we generated a high resolution linkage map from a family of 110 individuals and their parents by resequencing the individuals. 3,802 effective SNPs were mapped to 24 linkage groups (LGs). The map spanned 2,567.39 cm, with an average marker interval of 0.66 cm. We used the map to conduct QTL analysis for growth traits, and found 31 markers were significantly associated with growth-related traits...