The structure of vanin 1: a key enzyme linking metabolic disease and inflammation

Boersma, Ykelien L.; Newman, Janet; Adams, Timothy E.; Cowieson, Nathan; Krippner, Guy Y.; Bozaoglu, Kiymet; Peat, Thomas S.

doi:10.1107/s1399004714022767

Cited by 39 publications

(39 citation statements)

References 61 publications

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“…VNN is a glycosylphosphatidylinositol (GPI)-anchored protein [34] found at the surface of many different vertebrate cells [35] and may also be secreted [33]. GPI proteins perform diverse cellular functions, including lipid remodeling, which occurs during the replication of flaviviruses.…”

Section: Discussionmentioning

confidence: 99%

RNAi reveals proteins for metabolism and protein processing associated with Langat virus infection in Ixodes scapularis (black-legged tick) ISE6 cells

et al. 2017

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BackgroundTick-borne flaviviruses (TBFs) cause thousands of human cases of encephalitis worldwide each year, with some TBF infections progressing to hemorrhagic fever. TBFs are of medical and veterinary importance and strategies to reduce flavivirus transmission by the tick vector may have significant application. Analyses of the proteome of ISE6 cells derived from the black legged tick, Ixodes scapularis infected with the TBF, Langat virus (LGTV), have provided insights into proteins and cellular processes involved with LGTV infection.MethodsRNA interference (RNAi)-induced knockdown of transcripts was used to investigate the role of ten tick proteins in the LGTV infection cycle in ISE6 cells. LGTV-infected cells were separately transfected with dsRNA corresponding to each gene of interest and the effect on LGTV genome replication and release of infectious virus was assessed by RT-qPCR and plaque assays, respectively.ResultsRNAi-induced knockdown of transcripts for two enzymes that likely function in amino acid, carbohydrate, lipid, terpenoid/polykeytide and vitamin metabolism, and a transcript for one protein of unknown function were associated with decreased replication of the LGTV genome and release of infectious virus from cells. The knockdown of transcripts for five enzymes predicted to function in metabolism, a protein likely associated with folding, sorting and degradation, and a protein of unknown function was associated with a decrease only in the amount of infectious LGTV released from cells.ConclusionsThese data suggest tick proteins potentially associated with metabolism and protein processing may be involved in LGTV infection of ISE6 cells. Our study provides information to begin to elucidate the function of these proteins and identify targets for the development of new interventions aimed at controlling the transmission of TBFs.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1944-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

RNAi reveals proteins for metabolism and protein processing associated with Langat virus infection in Ixodes scapularis (black-legged tick) ISE6 cells

et al. 2017

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“…The neighborhood of SERPINC1 has been described above. VNN1 (Vanin 1) hydrolyzes specifically one of the carboamide linkages in D-pantetheine thus recycling pantothenic acid (vitamin B5) and releasing cysteamine, thus linking metabolic diseases and inflammation [69]. FN1 (Fibronectin 1) is involved in cell adhesion and migration processes including embryogenesis, wound healing, senescence [70], blood coagulation, host defense, and metastasis.…”

Section: Resultsmentioning

confidence: 99%

Proteome profiling in IL-1β and VEGF-activated human umbilical vein endothelial cells delineates the interlink between inflammation and angiogenesis

et al. 2017

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Endothelial cells represent major effectors in inflammation and angiogenesis, processes that drive a multitude of pathological states such as atherosclerosis and cancer. Both inflammation and angiogenesis are interconnected with each other in the sense that many pro-inflammatory proteins possess proangiogenic properties and vice versa. To elucidate this interplay further, we present a comparative proteome study of inflammatory and angiogenic activated endothelial cells. HUVEC were stimulated with interleukin 1-β and VEGF, respectively. Cultured primary cells were fractionated into secreted, cytoplasmic and nuclear protein fractions and processed for subsequent LC-MS/MS analysis. Obtained protein profiles were filtered for fraction-specific proteins to address potential cross fractional contamination, subjected to comparative computational biology analysis (GO-Term enrichment analysis, weighted gene co-expression analysis) and compared to published mRNA profiles of IL-1β respectively VEGF stimulated HUVEC. GO Term enrichment analysis and comparative pathway analysis revealed features such as NOD and NfkB signaling for inflammatory activated HUVEC and VEGF and ErB signaling for VEGF-activated HUVEC with potential crosstalk via map kinases MAP2K2. Weighted protein co-expression network analysis revealed several potential hub genes so far not associated with driver function in inflammation or angiogenesis such as HSPG2, ANXA3, and GPI. “Classical” inflammation or angiogenesis markers such as IL6, CXCL8 or CST1 were found in a less central position within the co-expression networks. In conclusion, this study reports a framework for the computational biology based analysis of proteomics data applied to cytoplasmic, nucleic and extracellular fractions of quiescent, inflammatory and angiogenic activated HUVEC. Novel potential hub genes relevant for these processes were successfully identified.

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“…The vanin-1 protein also has a so-called base domain, with a suggested role in binding to other proteins and in signaling, that regulates the enzymatic activity of vanins through allosteric movements [12]. Vanin-1 and vanin-2 genes have a region containing a glycosyl-phosphatidylinositol (GPI)-anchored cleavage site in exon 7 responsible for the attachment to the cell membrane through GPI anchoring [13,14].…”

Section: Introductionmentioning

confidence: 99%

Role of the Vanins–Myeloperoxidase Axis in Colorectal Carcinogenesis

Mariani

Roncucci

2017

IJMS

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The presence of chronic inflammation in the colonic mucosa leads to an increased risk of cancer. Among proteins involved in the regulation of mucosal inflammation and that may contribute both to structural damage of the intestinal mucosa and to intestinal carcinogenesis, there are myeloperoxidase (MPO) and vanins. The infiltration of colonic mucosa by neutrophils may promote carcinogenesis through MPO, a key enzyme contained in the lysosomes of neutrophils that regulates local inflammation and the generation of reactive oxygen species (ROS) and mutagenic species. The human vanin gene family consists of three genes: vanin-1, vanin-2 and vanin-3. All vanin molecules are pantetheinases, that hydrolyze pantetheine into pantothenic acid (vitamin B5), and cysteamine, a sulfhydryl compound. Vanin-1 loss confers an increased resistance to stress and acute intestinal inflammation, while vanin-2 regulates adhesion and transmigration of activated neutrophils. The metabolic product of these enzymes has a prominent role in the inflammation processes by affecting glutathione levels, inducing ulcers through a reduction in mucosal blood flow and oxygenation, decreasing local defense mechanisms, and in carcinogenesis by damaging DNA and regulating pathways involved in cell apoptosis, metabolism and growth, as Nrf2 and HIF-1α.

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The structure of vanin 1: a key enzyme linking metabolic disease and inflammation

Cited by 39 publications

References 61 publications

RNAi reveals proteins for metabolism and protein processing associated with Langat virus infection in Ixodes scapularis (black-legged tick) ISE6 cells

RNAi reveals proteins for metabolism and protein processing associated with Langat virus infection in Ixodes scapularis (black-legged tick) ISE6 cells

Proteome profiling in IL-1β and VEGF-activated human umbilical vein endothelial cells delineates the interlink between inflammation and angiogenesis

Role of the Vanins–Myeloperoxidase Axis in Colorectal Carcinogenesis

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