Novel function of FAXDC2 in megakaryopoiesis

Qi, Jin; Ren, Yujie; Wang, M; Suraneni, Praveen; Li, D; Crispino, John D.; Fan, Jingyi; Huang, Zan

doi:10.1038/bcj.2016.87

Cited by 29 publications

(20 citation statements)

References 23 publications

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“…However, we note that ATF4 may also be proviral (Caselli et al, 2012;Lee et al, 2018;Qian et al, 2012). Other low-TE genes include FAXDC2, STYX, SHOC2 which are involved in the Ras/Raf/Mitogen-activated protein kinase/ERK Kinase (MEK)/Extracellular-signal-Regulated Kinase (ERK) cascade (Jin et al, 2016;Reiterer et al, 2013;Rodriguez-Viciana et al, 2006). Importantly, it is commonly involved in viral infection, including that of coronaviruses (Kumar et al, 2018).…”

Section: Ribosome Profiling From Nsp1-expressing Cells Reveals Differmentioning

confidence: 99%

Genes with 5′ terminal oligopyrimidine tracts preferentially escape global suppression of translation by the SARS-CoV-2 Nsp1 protein

Rao

Hoskins

Garcia

et al. 2020

Preprint

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Viruses rely on the host translation machinery to synthesize their own proteins. Consequently, they have evolved varied mechanisms to co-opt host translation for their survival. SARS-CoV-2 relies on a non-structural protein, NSP1, for shutting down host translation. Despite this, it is currently unknown how viral proteins and host factors critical for viral replication can escape a global shutdown of host translation. Here, using a novel FACS-based assay called MeTAFlow, we report a dose-dependent reduction in both nascent protein synthesis and mRNA abundance in cells expressing NSP1. We perform RNA-Seq and matched ribosome profiling experiments to identify gene-specific changes both at the mRNA expression and translation level. We discover a functionally-coherent subset of human genes preferentially translated in the context of NSP1 expression. These genes include the translation machinery components, RNA binding proteins, and others important for viral pathogenicity. Importantly, we also uncover potential mechanisms of preferential translation through the presence of shared sites for specific RNA binding proteins and a remarkable enrichment for 5′ terminal oligo-pyrimidine tracts. Collectively, the present study suggests fine tuning of host gene expression and translation by NSP1 despite its global repressive effect on host protein synthesis.

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Section: Ribosome Profiling From Nsp1-expressing Cells Reveals Differmentioning

confidence: 99%

Genes with 5′ terminal oligopyrimidine tracts preferentially escape global suppression of translation by the SARS-CoV-2 Nsp1 protein

Rao

Hoskins

Garcia

et al. 2020

Preprint

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“…FAXDC2 belongs to the fatty acid hydroxylase superfamily that includes fatty acid and carotene hydroxylases and sterol desaturases, which are involved in cholesterol biosynthesis [27]. Specifically, fatty acid hydroxylase can alter the packing structures of membrane microdomains, and thus, regulates cellular function of membrane-associated proteins [28].…”

Section: Discussionmentioning

confidence: 99%

Expression of genes related to lipid transport in meat-type ducks divergent for low or high residual feed intake

Jin

Zang

et al. 2020

Asian-Australas J Anim Sci

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Objective: This study examined the effects of divergence in residual feed intake (RFI) on expression profiles of key genes related to lipid transport in the liver and duodenal epithelium and their associations with feed efficiency traits in meat-type ducks. Methods: A total of 1,000 male ducks with similar body weight (1,042.1±87.2 g) were used in this study, and their individual RFI was calculated from 21 to 42 d of age. Finally, the 10 highest RFI (HRFI) and 10 lowest RFI (LRFI) ducks were chosen for examining the expression of key genes related to lipid transport in the liver and duodenal epithelium using quantitative polymerase chain reaction. Results: In the liver, expression levels of albumin (ALB), CD36 molecule (CD36), fatty acid hydroxylase domain containing 2 (FAXDC2), and choline kinase alpha (CHKA) were significantly higher in LRFI ducks than in HRFI ducks (p<0.01); negative correlations (p<0.05) between expression levels of ALB, CD36, FAXDC2, and CHKA and RFI were detected in the liver. Additionally, ALB expression was strongly positively correlated (p<0.05) with CD36, FAXDC2, CHKA, and apolipoprotein H (APOH) expression in the liver. In duodenal epithelium, we found that mRNA levels of ALB, CD36, FAXDC2, and APOH were significantly higher in LRFI ducks than in HRFI ducks (p<0.01); RFI was strongly negatively correlated (p<0.05) with ALB, FAXDC2, and APOH expression, while ALB expression was strongly positively correlated with APOH expression (p<0.01) in duodenal epithelium. Furthermore, expression levels of both ALB and FAXDC2 genes were significantly associated with feed conversion ratio and RFI in both liver and duodenal epithelium (p<0.05). Conclusion: Our findings therefore suggest that ALB and FAXDC2 genes might be used as potential gene markers designed to improve feed efficiency in future meat-type duck breeding programs.

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“…CMK cells treatment with Nocodazole (10 ng/ml), Methotrexate (2.5 nM), Etoposide (10 μM), and TPA (50 nM) was carried out as previously described [14,18,[33][34][35]. Human megakaryocyte culture experiments were performed by culturing CD34 + cells (purchased from Fred Hutchinson Cancer Research Center, USA) in StemSpam SFEM media (Stemcell Technologies, Vancouver, BC, Canada) supplemented with penicillin/streptomycin and lipids (40 mg/ ml) as well as megakaryocyte differentiation cytokine cocktail containing stem cell factor (100 ng/ml) and TPO (10 ng/ml) for 10 days [35,36]. Culturing mouse megakaryocytes from fetal liver cells was carried out as previously described [37].…”

Section: Cell Culture Animals and Blood Samplesmentioning

confidence: 99%

BMP2K dysregulation promotes abnormal megakaryopoiesis in acute megakaryoblastic leukemia

Wang

Zhang

et al. 2020

Cell Biosci

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Background: Forced polyploidization is an effective strategy for acute megakaryoblastic leukemia (AMKL) therapy and factors controlling polyploidization are potential targets for drug development. Although bone morphology protein 2-inducible kinase (BMP2K) has been implied to be a potential target for fasudil, a potent polyploidy-inducing compound, the function of BMP2K in megakaryopoiesis and AMKL remains unknown. This study aimed to investigate the role of BMP2K as a novel regulator in megakaryocyte polyploidization and differentiation and its implication in AMKL therapy. Results: BMP2K upregulation was observed in human megakaryopoiesis and leukemia cells whereas BMP2K was downregulated in AMKL cells forced to undergo terminal differentiation. Functionally, BMP2K suppressed MLN8237-induced megakaryocytic differentiation in AMKL cells and dampened megakaryocyte differentiation in primary mouse fetal liver cells. Furthermore, BMP2K overexpression conferred resistance to multiple chemotherapy compounds in AMKL cells. Mechanistically, cyclin-dependent kinase 2 (CDK2) interacted with BMP2K and partially mediated its function. In transient MLN8237 and nocodazole challenge cell model, BMP2K reduced cell percentage of G2/M phase but increased G1 phase, suggesting a role of BMP2K antagonizing polyploidization and promoting mitosis by regulating cell cycle in megakaryopoiesis. Conclusions: BMP2K negatively regulates polyploidization and megakaryocyte differentiation by interacting CDK2 and promoting mitosis in megakaryopoiesis. BMP2K may serve as a potential target for improvement of AMKL therapy.

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Novel function of FAXDC2 in megakaryopoiesis

Cited by 29 publications

References 23 publications

Genes with 5′ terminal oligopyrimidine tracts preferentially escape global suppression of translation by the SARS-CoV-2 Nsp1 protein

Genes with 5′ terminal oligopyrimidine tracts preferentially escape global suppression of translation by the SARS-CoV-2 Nsp1 protein

Expression of genes related to lipid transport in meat-type ducks divergent for low or high residual feed intake

BMP2K dysregulation promotes abnormal megakaryopoiesis in acute megakaryoblastic leukemia

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