Molecular and functional characterization of granulin-like molecules of insects

Hanington, Patrick C.; Brennan, Lesley; Belosevic, Miodrag; Keddie, B. A.

doi:10.1016/j.ibmb.2008.02.002

Cited by 13 publications

(11 citation statements)

References 19 publications

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“…Large progranulin is post-translationally processed into different granulins to mediate various physiological processes such as cell cycling, wound healing, and brain development [65]. In insects, granulin-like molecules have been reported in locust ( Schistocerca gregaria ), mosquito ( Aedes albopictus ), and moth ( Manduca sexta ) with cell proliferating activity [66]. With respect to gene expression control, granulin is known to be able to activate PKC pathway and Toll-like receptor 9 signaling or interact with transcriptional factor such as STAT3 in breast cancer cells [67,68].…”

Section: Discussionmentioning

confidence: 99%

Translational Control of Host Gene Expression by a Cys-Motif Protein Encoded in a Bracovirus

Kim

2016

PLoS ONE

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Translational control is a strategy that various viruses use to manipulate their hosts to suppress acute antiviral response. Polydnaviruses, a group of insect double-stranded DNA viruses symbiotic to some endoparasitoid wasps, are divided into two genera: ichnovirus (IV) and bracovirus (BV). In IV, some Cys-motif genes are known as host translation-inhibitory factors (HTIF). The genome of endoparasitoid wasp Cotesia plutellae contains a Cys-motif gene (Cp-TSP13) homologous to an HTIF known as teratocyte-secretory protein 14 (TSP14) of Microplitis croceipes. Cp-TSP13 consists of 129 amino acid residues with a predicted molecular weight of 13.987 kDa and pI value of 7.928. Genomic DNA region encoding its open reading frame has three introns. Cp-TSP13 possesses six conserved cysteine residues as other Cys-motif genes functioning as HTIF. Cp-TSP13 was expressed in Plutella xylostella larvae parasitized by C. plutellae. C. plutellae bracovirus (CpBV) was purified and injected into non-parasitized P. xylostella that expressed Cp-TSP13. Cp-TSP13 was cloned into a eukaryotic expression vector and used to infect Sf9 cells to transiently express Cp-TSP13. The synthesized Cp-TSP13 protein was detected in culture broth. An overlaying experiment showed that the purified Cp-TSP13 entered hemocytes. It was localized in the cytosol. Recombinant Cp-TSP13 significantly inhibited protein synthesis of secretory proteins when it was added to in vitro cultured fat body. In addition, the recombinant Cp-TSP13 directly inhibited the translation of fat body mRNAs in in vitro translation assay using rabbit reticulocyte lysate. Moreover, the recombinant Cp-TSP13 significantly suppressed cellular immune responses by inhibiting hemocyte-spreading behavior. It also exhibited significant insecticidal activities by both injection and feeding routes. These results indicate that Cp-TSP13 is a viral HTIF.

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Section: Discussionmentioning

confidence: 99%

Translational Control of Host Gene Expression by a Cys-Motif Protein Encoded in a Bracovirus

Kim

2016

PLoS ONE

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“…The ubiquitous expression of Ov -GRN-1 in organs and tissues of adult O. viverrini (Smout et al, 2009) supports the notion that this fluke mitogen functions as an essential, endogenous growth factor for O. viverrini . It is not unexpected that Ov -GRN-1 functions as a growth factor for both the liver fluke and its host cells since granulins evolved in all branches of the animal kingdom and are known to promote proliferation of different cell types from phylogenetically distant taxa (Hanington et al, 2008). Future studies will explore the effects of introducing Ov-grn-1 dsRNA-treated metacercariae (the infectious stage to mammals) to hamsters to assess survival in vivo .…”

Section: Discussionmentioning

confidence: 99%

Suppression of Ov-grn-1 encoding granulin of Opisthorchis viverrini inhibits proliferation of biliary epithelial cells

Papatpremsiri

Smout

Loukas

et al. 2015

Experimental Parasitology

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Multistep processes likely underlie cholangiocarcinogenesis induced by chronic infection with the fish-borne liver fluke, Opisthorchis viverrini. One process appears to be cellular proliferation of the host bile duct epithelia driven by excretory-secretory (ES) products of this pathogen. Specifically, the secreted growth factor Ov-GRN-1, a liver fluke granulin, is a prominent component of ES and a known driver of hyper-proliferation of cultured human and mouse cells in vitro. We show potent hyper-proliferation of human cholangiocytes induced by low nanomolar levels of recombinant Ov-GRN-1 and similar growth produced by low microgram concentrations of ES products and soluble lysates of the adult worm. To further explore the influence of Ov-GRN-1 on the flukes and the host cells, expression of Ov-grn-1 was repressed using RNA interference. Expression of Ov-grn-1 was suppressed by 95% by day 3 and by ~100% by day 7. Co-culture of Ov-grn-1 suppressed flukes with human cholangiocyte (H-69) or human cholangiocarcinoma (KKU-M214) cell lines retarded cell hyper-proliferation by 25% and 92%, respectively. Intriguingly, flukes in which expression of Ov-grn-1 was repressed were less viable in culture, suggesting that Ov-GRN-1 is an essential growth factor for survival of the adult stage of O. viverrini survival, at least in vitro. To summarize, specific knock down of Ov-grn-1 reduced in vitro survival and capacity of ES products to drive host cell proliferation. These findings may help to contribute to a deeper understanding of liver fluke induced cholangiocarcinogenesis.

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“…Granulins were initially identified in the granules of human leukocytes and are now known to occur in a wide range of organisms with examples in particular species of oyster, insects, parasites, ascidians, mollusks, and plants . They are involved in several physiological functions and disease processes such as cell growth modulatory effects, wound repair, inflammation, and tumor growth .…”

Section: Introduction—granulinsmentioning

confidence: 99%

Folding of granulin domains

et al. 2018

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Granulins are a family of protein growth factors that are involved in a range of biological functions, including wound repair, inflammation, and tumor growth. They are often expressed as part of large precursor proteins containing multiple granulin domains. Individual granulin domains are characterized by a conserved arrangement of 12 cysteine residues that form six disulfide bonds. Despite the conservation of the cysteine residues, there is significant sequence variation between granulins from different species. The initial structure determined for this family indicated the presence of a well‐defined structure with a laddered arrangement of the six disulfide bonds and a β‐hairpin stack. However, subsequent studies have shown the structure‐function relationships of granulins are quite complex. Recent studies have indicated some granulins might have potential as wound healing agents, and studies aimed at understanding the structure‐function relationships of this family are likely to enhance this potential in drug design. This review provides an overview of the structure‐based studies of granulins, including the folding of truncated peptides derived from granulins from different species.

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Molecular and functional characterization of granulin-like molecules of insects

Cited by 13 publications

References 19 publications

Translational Control of Host Gene Expression by a Cys-Motif Protein Encoded in a Bracovirus

Translational Control of Host Gene Expression by a Cys-Motif Protein Encoded in a Bracovirus

Suppression of Ov-grn-1 encoding granulin of Opisthorchis viverrini inhibits proliferation of biliary epithelial cells

Folding of granulin domains

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