Publications by authors named "Anurupa Dev"

6 Publications

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A TRAF3-NIK module differentially regulates DNA vs RNA pathways in innate immune signaling.

Nat Commun 2018 07 17;9(1):2770. Epub 2018 Jul 17.

Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, 90095, USA.

Detection of viral genomes by the innate immune system elicits an antiviral gene program mediated by type I interferons (IFNs). While viral RNA and DNA species induce IFN via separate pathways, the mechanisms by which these pathways are differentially modulated are unknown. Here we show that the positive regulator of IFN in the RNA pathway, TRAF3, has an inhibitory function in the DNA pathway. Loss of TRAF3 coincides with increased expression of the alternative NF-κB-inducing molecule, NIK, which interacts with the DNA pathway adaptor, STING, to enhance IFN induction. Cells lacking NIK display defective IFN activation in the DNA pathway due to impaired STING signaling, and NIK-deficient mice are more susceptible to DNA virus infection. Mechanistically, NIK operates independently from alternative NF-κB signaling components and instead requires autophosphorylation and oligomerization to activate STING. Thus a previously undescribed pathway for NIK exists in activating IFN in the DNA pathway.
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http://dx.doi.org/10.1038/s41467-018-05168-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050272PMC
July 2018

The U.S. Public's Investment in Medical Research: An Evolving Social Contract.

Am J Med Sci 2016 Jan;351(1):69-76

Association of American Medical Colleges, Washington, DC.

Medical researchers and their institutions are operating under extraordinary financial stress. More than a decade after completion of the 5-year doubling of the National Institutes of Health budget, the medical research community must confront a significant loss in National Institutes of Health purchasing power and downward pressures in federal discretionary spending. In part, this trend results from a federal budget stalemate over the growth in entitlement programs, particularly spending on medical care. This article considers the changing nature of the federal investment in medical research and the potential for medical researchers and institutions conducting the full spectrum of research to improve health system performance and health equity. In our view, continued federal investments reflect an evolving social contract for research serving the public good; the term contract is used metaphorically to represent a figurative, implicit agreement between the scientific community and the public's representatives in government. Under this conceptual contract, the American people--who are ultimately the funders of research, research training and infrastructure--expect outcomes that lead to better health, security or other benefits. The evolving contract includes expectations for more accountability, transparency, sharing of results and resources, and better integration of research systems and cultures that used to take pride in boundaries and distinctions. We outline here some of the major movements of organizations realigning to social support, which are increasingly essential to sustain public investment in medical research.
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http://dx.doi.org/10.1016/j.amjms.2015.10.016DOI Listing
January 2016

NF-κB and innate immunity.

Curr Top Microbiol Immunol 2011 ;349:115-43

Department of Microbiology, Immunology & Molecular Genetics, University of California Los Angeles, 615 Charles Young Dr S., 210A BSRB, Los Angeles, CA 90095, USA.

Members of the NF-κB transcription factor family play a critical role in the development of innate immunity. Upon recognition of pathogen infections or tissue damage, the NF-κB pathway is strongly activated by cellular pattern recognition receptors, including Toll-like receptors and multiple cytosolic receptors such as RIG-I-like helicases and NOD family proteins. NF-κB is required not only for the expression, but also for subsequent signal transduction of numerous downstream cytokines. NF-κB-responsive genes affect a diverse array of cellular processes including apoptosis and cell survival, and often directly control the course of a pathogen infection. In this review, we will examine signaling pathways leading to NF-κB activation during the innate immune response and mechanisms of pathogen-modulation of these pathways; the specifics of NF-κB-dependent gene programs, and the physiological consequences for the immune system caused by the absence of individual NF-κB subunits.
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http://dx.doi.org/10.1007/82_2010_102DOI Listing
August 2011

Indole-3-carbinol mediated cell cycle arrest of LNCaP human prostate cancer cells requires the induced production of activated p53 tumor suppressor protein.

Biochem Pharmacol 2006 Dec 12;72(12):1714-23. Epub 2006 Sep 12.

Department of Molecular and Cell Biology and The Cancer Research Laboratory, The University of California at Berkeley, Berkeley, CA 94720, USA.

Indole-3-carbinol (I3C), a dietary compound found naturally in cruciferous vegetables of the Brassica genus such as broccoli and brussels sprouts, induces a G1 growth arrest of human reproductive cancer cells. We previously reported that in LNCaP prostate cancer cells, I3C down-regulated cyclin-dependent kinase (CDK) 2 activity. In our current study, Western blotting and quantitative RT-PCR demonstrated that I3C treatment increased both the transcripts and protein levels of the CDK2 inhibitor p21(waf1/cip1) (p21). Transfection of luciferase reporter plasmids containing wild-type and mutated p21 promoter fragments revealed that I3C induced p21 gene transcription through a p53 DNA binding element. Oligonucleotide precipitation showed that I3C increased the level of activated p53 nuclear protein that is competent to bind its DNA target site on the p21 promoter. Ablation of p53 production using short interfering RNA (siRNA) prevented that the I3C induced G1 arrest and up-regulation of p21 expression. Western blots using p53 phospho-specific antibodies revealed that I3C treatment increased the levels of three phosphorylated forms of p53 (Ser15, Ser37, Ser392) that are known to contribute to p53 protein stability and greater transactivation potential. Taken together, our results establish that the I3C induced G1 arrest of human prostate cancer cells requires the induced production of the activated phosphorylated forms of p53, which stimulate transcription of the CDK2 inhibitor p21.
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http://dx.doi.org/10.1016/j.bcp.2006.08.012DOI Listing
December 2006

Indole-3-carbinol inhibition of androgen receptor expression and downregulation of androgen responsiveness in human prostate cancer cells.

Carcinogenesis 2005 Nov 15;26(11):1896-904. Epub 2005 Jun 15.

Department of Molecular and Cell Biology, The University of California at Berkeley, CA 94720, USA.

Indole-3-carbinol (I3C), a naturally occurring compound found in vegetables of the Brassica genus, such as broccoli and cabbage, is a promising anticancer agent previously shown to induce a G(1) cell-cycle arrest in the cells of human lymph node carcinoma of prostate (LNCaP) through regulation of specific G(1)-acting cell-cycle components. Since the androgen receptor (AR) mediates proliferation and differentiation in the prostate and is expressed in nearly all human prostate cancers, the effects of I3C on AR expression and function were examined in LNCaP cells. Immunoblot and quantitative RT-PCR assays revealed that I3C inhibited the expression of AR protein and mRNA levels within 12 h of indole treatment. I3C downregulated the reporter activity of LNCaP cells transiently transfected with an AR promoter-luciferase plasmid, demonstrating that a unique response to I3C is the inhibition of AR promoter activity. In contrast to I3C, the natural I3C dimerization product 3,3'-diindolylmethane, which acts as an androgen antagonist, had no effect on AR expression. To determine the functional significance of the I3C-inhibited expression of AR, the AR-regulated prostate specific antigen (PSA) was utilized as a downstream indicator. I3C downregulated the expression of PSA transcripts and protein levels and inhibited PSA promoter activity, as well as that of a minimal androgen responsive element containing reporter plasmid. Expression of exogenous AR prevented the I3C disruption of androgen-induced PSA expression. Taken together, our results demonstrate that I3C represses AR expression and responsiveness in LNCaP cells as a part of its antiproliferative mechanism.
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http://dx.doi.org/10.1093/carcin/bgi155DOI Listing
November 2005