Author
Jeffry R. Cook
Other affiliations: Rutgers University
Bio: Jeffry R. Cook is an academic researcher from University of Medicine and Dentistry of New Jersey. The author has contributed to research in topics: Protein arginine methyltransferase 5 & Signal transduction. The author has an hindex of 16, co-authored 20 publications receiving 2129 citations. Previous affiliations of Jeffry R. Cook include Rutgers University.
Papers
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TL;DR: PRMT5 is the first example of a catalytic chain for a type II protein arginine N-methyltransferase that can result in the formation of symmetric dimethylarginine residues as observed previously in myelin basic protein, Sm small nuclear ribonucleoproteins, and other polypeptides.
354 citations
TL;DR: Because of the intricate involvement of several PRMT in cellular physiology, their inhibition may be fraught with unwanted side effects, Nevertheless, development of pharmaceutical agents to control PRMT functions could lead to significant new targets.
282 citations
TL;DR: It is confirmed that an additional factor encoded on human chromosome 21 is required for reconstitution of antiviral activity against EMCV, and that this accessory factor belongs to a family of such accessory factors responsible for different actions of IFN-γ.
257 citations
TL;DR: Ch Chromatin immunoprecipitations show that PRMT5 is associated specifically with the transcription start site region of the cyclin E1 promoter, providing the first direct experimental evidence that a type II arginine methylase is involved in the control of transcription and proliferation.
Abstract: We have identified previously a repressor element in the transcription start site region of the cyclin E1 promoter that periodically associates with an atypical, high molecular weight E2F complex, termed CERC. Purification of native CERC reveals the presence of the type II arginine methyltransferase PRMT5, which can mono- or symetrically dimethylate arginine residues in proteins. Chromatin immunoprecipitations (ChIPs) show that PRMT5 is associated specifically with the transcription start site region of the cyclin E1 promoter. ChIP analyses also show that this correlates with the presence on the same promoter region of arginine-methylated proteins including histone H4, an in vitro substrate of PRMT5. Consistent with its presence within the repressor complex, forced expression of PRMT5 negatively affects cyclin E1 promoter activity and cellular proliferation, effects that require its methyltransferase activity. These data provide the first direct experimental evidence that a type II arginine methylase is involved in the control of transcription and proliferation.
232 citations
TL;DR: The cDNA for PRMT7, a recently discovered human protein-arginine methyltransferase (PRMT), was cloned and expressed in Escherichia coli and mammalian cells, demonstrating thatPRMT7 (like PRMT5) is a Type II methyl transferase capable of producing SDMA modifications in proteins.
212 citations
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TL;DR: A previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that phosphorylate substrate proteins called STATs (signal transducers and activators of transcription).
Abstract: Through the study of transcriptional activation in response to interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma), a previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that then phosphorylate substrate proteins called STATs (signal transducers and activators of transcription). The phosphorylated STAT proteins move to the nucleus, bind specific DNA elements, and direct transcription. Recognition of the molecules involved in the IFN-alpha and IFN-gamma pathway has led to discoveries that a number of STAT family members exist and that other polypeptide ligands also use the Jak-STAT molecules in signal transduction.
5,746 citations
TL;DR: The Janus kinases and signal transducers and activators of transcription, and many of the interferon-induced proteins, play important alternative roles in cells, raising interesting questions as to how the responses to the interFERons intersect with more general aspects of cellular physiology and how the specificity of cytokine responses is maintained.
Abstract: Interferons play key roles in mediating antiviral and antigrowth responses and in modulating immune response. The main signaling pathways are rapid and direct. They involve tyrosine phosphorylation and activation of signal transducers and activators of transcription factors by Janus tyrosine kinases at the cell membrane, followed by release of signal transducers and activators of transcription and their migration to the nucleus, where they induce the expression of the many gene products that determine the responses. Ancillary pathways are also activated by the interferons, but their effects on cell physiology are less clear. The Janus kinases and signal transducers and activators of transcription, and many of the interferon-induced proteins, play important alternative roles in cells, raising interesting questions as to how the responses to the interferons intersect with more general aspects of cellular physiology and how the specificity of cytokine responses is maintained.
4,026 citations
TL;DR: The current understanding of IFN‐γ ligand, receptor, ignal transduction, and cellular effects with a focus on macrophage responses and to a lesser extent, responses from other cell types that influence macrophages function during infection are reviewed.
Abstract: Interferon-gamma (IFN-gamma) coordinates a diverse array of cellular programs through transcriptional regulation of immunologically relevant genes. This article reviews the current understanding of IFN-gamma ligand, receptor, signal transduction, and cellular effects with a focus on macrophage responses and to a lesser extent, responses from other cell types that influence macrophage function during infection. The current model for IFN-gamma signal transduction is discussed, as well as signal regulation and factors conferring signal specificity. Cellular effects of IFN-gamma are described, including up-regulation of pathogen recognition, antigen processing and presentation, the antiviral state, inhibition of cellular proliferation and effects on apoptosis, activation of microbicidal effector functions, immunomodulation, and leukocyte trafficking. In addition, integration of signaling and response with other cytokines and pathogen-associated molecular patterns, such as tumor necrosis factor-alpha, interleukin-4, type I IFNs, and lipopolysaccharide are discussed.
3,589 citations
TL;DR: Drawing on insights from both plants and animals should deepen the understanding of the regulation and biological significance of DNA methylation.
Abstract: Cytosine DNA methylation is a stable epigenetic mark that is crucial for diverse biological processes, including gene and transposon silencing, imprinting and X chromosome inactivation. Recent findings in plants and animals have greatly increased our understanding of the pathways used to accurately target, maintain and modify patterns of DNA methylation and have revealed unanticipated mechanistic similarities between these organisms. Key roles have emerged for small RNAs, proteins with domains that bind methylated DNA and DNA glycosylases in these processes. Drawing on insights from both plants and animals should deepen our understanding of the regulation and biological significance of DNA methylation.
3,180 citations
TL;DR: It is anticipated that an increased understanding of the contributions of these recently identified pathways will advance current thinking about how interferons work.
Abstract: Interferons are cytokines that have antiviral, antiproliferative and immunomodulatory effects. Because of these important properties, in the past two decades, major research efforts have been undertaken to understand the signalling mechanisms through which these cytokines induce their effects. Since the original discovery of the classical JAK (Janus activated kinase)-STAT (signal transducer and activator of transcription) pathway of signalling, it has become clear that the coordination and cooperation of multiple distinct signalling cascades - including the mitogen-activated protein kinase p38 cascade and the phosphatidylinositol 3-kinase cascade - are required for the generation of responses to interferons. It is anticipated that an increased understanding of the contributions of these recently identified pathways will advance our current thinking about how interferons work.
2,912 citations