Cloning of DLM-1, a novel gene that is up-regulated in activated macrophages, using RNA differential display

Fu, Yang; Comella, Natalia; Tognazzi, Kathi; Brown, Lawrence F.; Dvorak, Harold F.; Kocher, Olivier

doi:10.1016/s0378-1119(99)00419-9

Cited by 134 publications

(101 citation statements)

References 17 publications

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“…These proteins contain one or more domains that can interact with a Z-DNA structure and thereby specifically stabilize and induce Z-DNA and Z-RNA conformation. At present only a handful of such proteins have been identified, and these include the RNA editing enzyme ADAR1 (38), DNA-dependent activator of IFN-regulatory factor (DAI/ZBP1/DLM-1) (27,39,40), vaccinia virus Z-DNA-binding protein E3L (28,41), and zebrafish PKRlike protein kinase (42). Some of the Z-DNA-binding proteins are inducible in nature and have been shown to play a critical role in the host response against tumors and in the activation of innate immune response (39,40,43).…”

Section: Discussionmentioning

confidence: 99%

Z-DNA-forming silencer in the first exon regulates human ADAM-12 gene expression

Ray

Dhar

Shakya

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Upregulation of ADAM-12, a novel member of the multifunctional ADAM family of proteins is linked to cancer, arthritis and cardiac hypertrophy. Basal expression of ADAM-12 is very low in adult tissues but rises markedly in response to certain physiological cues, such as during pregnancy in the placenta, during development in neonatal skeletal muscle and bone and in regenerating muscle. Studies on ADAM-12 regulation have identified a highly conserved negative regulatory element (NRE) at the 5′-UTR of human ADAM-12 gene, which acts as a transcriptional repressor. The NRE contains a stretch of dinucleotide-repeat sequence that is able to adopt a Z-DNA conformation both in vitro and in vivo and interacts with hZα ADAR1 , a bona fide Z-DNA-binding protein. Substitution of the dinucleotide-repeat-element with a non-Z-DNA-forming sequence inhibited NRE function. We have detected a NRE DNA-binding protein activity in several tissues where ADAM-12 expression is low while no such activity was seen in the placenta where ADAM-12 expression is high. These observations suggest that interaction of these proteins with ADAM-12 NRE is critical for transcriptional repression of ADAM-12. We also show that the Z-DNA forming transcriptional repressor element, by interacting with these putative Z-DNA-binding proteins, is involved in the maintenance of constitutive low-level expression of human ADAM-12. Together these results provide a foundation for therapeutic down-regulation of ADAM-12 in cancer, arthritis and cardiac hypertrophy.

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Section: Discussionmentioning

confidence: 99%

Z-DNA-forming silencer in the first exon regulates human ADAM-12 gene expression

Ray

Dhar

Shakya

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…ZBP1 is strongly induced by interferons and LPS (ref. 36 and N.D., unpublished data) and its expression is tightly associated with inhibition of hepatitis B virus replication (37). Human ADAR1 has differently regulated isoforms: a constitutively expressed isoform lacking the Z␣ domain and a larger, IFN-induced form, which contains Z␣ (38).…”

Section: Fig 2 Expression Pattern Of Pkz 12 H After Induction By Pomentioning

confidence: 99%

A PKR-like eukaryotic initiation factor 2α kinase from zebrafish contains Z-DNA binding domains instead of dsRNA binding domains

Rothenburg

Deigendesch

Dittmar

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

157

196

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The double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is induced as part of the IFN response in mammals and acts to shut down protein synthesis by the phosphorylation of eukaryotic initiation factor 2␣ (eIF2␣). In fish, a PKR-like kinase activity has been detected, but the enzyme responsible has eluded characterization. Here, we describe a PKR-like kinase from zebrafish. Phylogenetic analysis shows that the C-terminal kinase domain is more closely related to the kinase domain of PKR than to any of the other three known eIF2␣ kinases. Surprisingly, instead of the two dsRNA binding domains found at the N terminus of PKR, there are two Z␣ domains. Z␣ domains specifically bind dsDNA and RNA in the left-handed Z conformation, often with high affinity. They have been found previously in two other IFN-inducible proteins, the dsRNA editing enzyme, ADAR1, and Z-DNA binding protein 1 (ZBP1), as well as in the poxvirus virulence factor, E3L. This previously undescribed kinase, designated PKZ (protein kinase containing Z-DNA binding domains), is transcribed constitutively at low levels and is highly induced after injection of poly(inosinic)-poly(cytidylic) acid, which simulates viral infection. Binding of Z-DNA by the Z␣ domain of PKZ was demonstrated by circular dichroism. PKZ inhibits translation in transfected cells; site-directed mutagenesis indicates that this inhibition depends on its catalytic activity. Identification of a gene combining Z␣ domains with a PKR-like kinase domain strengthens the hypothesis that the ability to bind left-handed nucleic acid plays a role in the host response to viruses.E3L ͉ interferon response ͉ viral infection ͉ Z-RNA ͉ Z␣ domain

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“…NA-dependent activator of interferon (IFN) regulatory factor (DAI), which is also referred to as Z-DNA binding protein 1 (ZBP1) or DLM-1, was initially identified as a highly upregulated protein in mouse tumor stromal cells and in macrophages treated by gamma IFN (IFN-␥) or lipopolysaccharide (1). Structural analyses have revealed that DAI/ZBP1/DLM-1 (referred to as DAI hereafter) contains the amino-terminal Z-form DNA-binding domains, Z␣ and Z␤, which are homologous to those of adenosine deaminase that acts on RNA (ADAR1), an RNA editing enzyme (2)(3)(4)(5).…”

mentioning

confidence: 99%

DNA Sensing-Independent Inhibition of Herpes Simplex Virus 1 Replication by DAI/ZBP1

Pham

Kwon

Kim

et al. 2013

J Virol

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DNA-dependent activator of interferon regulatory factor (DAI) acts as a cytosolic B-form DNA sensor that induces type I interferons. However, DAI is not required for DNA sensing in certain cell types due to redundancy of the DNA sensing system. Here, we investigated the effect of DAI on herpes simplex virus 1 (HSV-1) infection in HepG2 hepatocellular carcinoma cells. DAI transcription was induced after gamma interferon (IFN-␥) treatment or HSV-1 infection. HSV-1 replication was enhanced by DAI knockdown, and ectopic DAI expression repressed viral replication in a manner requiring the Z␤ and D3 domains, but not the Z␣ domain. This activity of DAI was more prominent at low multiplicity of infection (MOI) and correlated with the reduced expression of viral immediate-early genes. Consistently, DAI repressed the activation of ICP0 promoter in reporter gene assays. DNA-dependent activator of interferon (IFN) regulatory factor (DAI), which is also referred to as Z-DNA binding protein 1 (ZBP1) or DLM-1, was initially identified as a highly upregulated protein in mouse tumor stromal cells and in macrophages treated by gamma IFN (IFN-␥) or lipopolysaccharide (1). Structural analyses have revealed that DAI/ZBP1/DLM-1 (referred to as DAI hereafter) contains the amino-terminal Z-form DNA-binding domains, Z␣ and Z␤, which are homologous to those of adenosine deaminase that acts on RNA (ADAR1), an RNA editing enzyme (2-5). Since Z-DNA is located near the transcription start sites of certain genes in the genome, a role of DAI in transcriptional regulation has been suggested (6, 7). Induction of DAI was also observed in mouse hepatocytes infected with hepatitis B virus (HBV) (8) and in mouse embryonic fibroblasts (MEFs) stimulated by B-form DNA (9).Recently, DAI was shown to act as a cytosolic B-form DNA sensor that initiates IFN responses via activation of the nuclear factor-B (NF-B) and interferon regulatory transcription factor 3 (IRF3) pathways in mice (10). In addition to the Z-DNA-binding domains, a region termed the D3 domain was demonstrated to primarily contribute to the recognition of B-DNA in vitro (10). However, all of the Z␣, Z␤, and D3 domains were required for efficient B-DNA binding in vivo and DAI was suggested to undergo DNA-mediated multimerization to evoke activation of IFN responses (11). The carboxyl-terminal region of DAI was responsible for recruitment of both IRF3 and TANK-binding kinase 1 (TBK1), an IB kinase that activates IRF3 (10). The mechanism by which DAI activates the NF-B pathway was shown to involve recruitment of receptor-interacting protein kinase 1 (RIP1) and RIP3 through a RIP homotypic interaction motif (RHIM)-dependent interaction with DAI (12, 13). Recently, the binding of DAI with RIP3 was shown to mediate virus-induced programmed necrosis (14).The requirement of DAI in induction of IFN response by cytosolic stimulation of B-DNA is dependent on cell type. DAI played a role in the DNA-mediated IFN production in mouse fibroblast L929 (10, 12, 15) and mouse SVEC4-10 endothelial cells (12)...

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Cloning of DLM-1, a novel gene that is up-regulated in activated macrophages, using RNA differential display

Cited by 134 publications

References 17 publications

Z-DNA-forming silencer in the first exon regulates human ADAM-12 gene expression

Z-DNA-forming silencer in the first exon regulates human ADAM-12 gene expression

A PKR-like eukaryotic initiation factor 2α kinase from zebrafish contains Z-DNA binding domains instead of dsRNA binding domains

DNA Sensing-Independent Inhibition of Herpes Simplex Virus 1 Replication by DAI/ZBP1

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