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Article: Protein kinase C in the transduction of signals toward and within the cell nucleus.

Buchner, K

1995 Volume 228, Issue 2, Page(s) 211–221

MeSH term(s)	Animals ; Biological Transport ; Calcium/metabolism ; Cell Nucleus/metabolism ; Diglycerides/biosynthesis ; Humans ; Isoenzymes/analysis ; Phosphorylation ; Protein Kinase C/analysis ; Protein Kinase C/physiology ; Signal Transduction
Chemical Substances	Diglycerides ; Isoenzymes ; Protein Kinase C (EC 2.7.11.13) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	1995-03-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	3032-6
ISSN	1432-1033 ; 0014-2956
ISSN (online)	1432-1033
ISSN	0014-2956
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Article ; Online: Protein kinase C signaling "in" and "to" the nucleus: Master kinases in transcriptional regulation.

Kazanietz, Marcelo G / Cooke, Mariana

The Journal of biological chemistry

2024 Volume 300, Issue 3, Page(s) 105692

Abstract: ... understanding of PKC signaling "in" and "to" the nucleus, with significant focus on established paradigms of PKC ... Notwithstanding their primary cytoplasmic localization and stringent activation by cell surface receptors, PKC isozymes impel ... activation of transcription factors implicated in cell cycle/mitogenesis, epithelial-to-mesenchymal transition and immune function ...

Abstract	PKC is a multifunctional family of Ser-Thr kinases widely implicated in the regulation of fundamental cellular functions, including proliferation, polarity, motility, and differentiation. Notwithstanding their primary cytoplasmic localization and stringent activation by cell surface receptors, PKC isozymes impel prominent nuclear signaling ultimately impacting gene expression. While transcriptional regulation may be wielded by nuclear PKCs, it most often relies on cytoplasmic phosphorylation events that result in nuclear shuttling of PKC downstream effectors, including transcription factors. As expected from the unique coupling of PKC isozymes to signaling effector pathways, glaring disparities in gene activation/repression are observed upon targeting individual PKC family members. Notably, specific PKCs control the expression and activation of transcription factors implicated in cell cycle/mitogenesis, epithelial-to-mesenchymal transition and immune function. Additionally, PKCs isozymes tightly regulate transcription factors involved in stepwise differentiation of pluripotent stem cells toward specific epithelial, mesenchymal, and hematopoietic cell lineages. Aberrant PKC expression and/or activation in pathological conditions, such as in cancer, leads to profound alterations in gene expression, leading to an extensive rewiring of transcriptional networks associated with mitogenesis, invasiveness, stemness, and tumor microenvironment dysregulation. In this review, we outline the current understanding of PKC signaling "in" and "to" the nucleus, with significant focus on established paradigms of PKC-mediated transcriptional control. Dissecting these complexities would allow the identification of relevant molecular targets implicated in a wide spectrum of diseases.
MeSH term(s)	Gene Expression Regulation/genetics ; Isoenzymes/genetics ; Isoenzymes/metabolism ; Protein Kinase C/genetics ; Protein Kinase C/metabolism ; Signal Transduction ; Transcription Factors/metabolism ; Humans ; Animals ; Cell Nucleus/enzymology ; Cell Nucleus/genetics
Chemical Substances	Isoenzymes ; Protein Kinase C (EC 2.7.11.13) ; Transcription Factors
Language	English
Publishing date	2024-01-30
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2024.105692
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Article ; Online: Interferon inducible guanylate-binding protein 1 modulates the lipopolysaccharide-induced cytokines/chemokines and mitogen-activated protein kinases in macrophages.

Kumar, Ravindra / Kushawaha, Pramod Kumar

Microbiology and immunology

2024 Volume 68, Issue 5, Page(s) 185–195

Abstract: ... the extracellular-signal-regulated kinase 1/2 mitogen-activated protein (MAP) kinases and signal transducer and activator of transcription 1 ... histocompatibility 2, class II antigen A, protein kinase R, and chemokines (chemokine (C-X-C motif) ligand 9 [CXCL9 ... cells. However, no change in the level of phosphorylated nuclear factor-kB, c-Jun, and p38 ...

Abstract	Guanylate-binding proteins (GBPs) are a family of interferon (IFN)-inducible GTPases and play a pivotal role in the host immune response to microbial infections. These are upregulated in immune cells after recognizing the lipopolysaccharides (LPS), the major membrane component of Gram-negative bacteria. In the present study, the expression pattern of GBP1-7 was initially mapped in phorbol 12-myristate 13-acetate-differentiated human monocytes THP-1 and mouse macrophages RAW 264.7 cell lines stimulated with LPS. A time-dependent significant expression of GBP1-7 was observed in these cells. Moreover, among the various GBPs, GBP1 has emerged as a central player in regulating innate immunity and inflammation. Therefore, to study the specific role of GBP1 in LPS-induced inflammation, knockdown of the Gbp1 gene was carried out in both cells using small interfering RNA interference. Altered levels of different cytokines (interleukin [IL]-4, IL-10, IL-12β, IFN-γ, tumor necrosis factor-α), inducible nitric oxide synthase, histocompatibility 2, class II antigen A, protein kinase R, and chemokines (chemokine (C-X-C motif) ligand 9 [CXCL9], CXCL10, and CXCL11) in GBP1 knockdown cells were reported compared to control cells. Interestingly, the extracellular-signal-regulated kinase 1/2 mitogen-activated protein (MAP) kinases and signal transducer and activator of transcription 1 (STAT1) transcription factor levels were considerably induced in knockdown cells compared to the control cells. However, no change in the level of phosphorylated nuclear factor-kB, c-Jun, and p38 transcription factors was observed in GBP1 knockdown cells compared to the control cells. This study concludes that GBP1 may alter the expression of cytokines, chemokines, and effector molecules mediated by MAP kinases and STAT1 transcription factors.
MeSH term(s)	GTP-Binding Proteins/genetics ; GTP-Binding Proteins/metabolism ; Humans ; Macrophages/immunology ; Macrophages/metabolism ; Mice ; Animals ; Lipopolysaccharides/pharmacology ; Cytokines/metabolism ; RAW 264.7 Cells ; STAT1 Transcription Factor/metabolism ; STAT1 Transcription Factor/genetics ; Chemokines/metabolism ; Mitogen-Activated Protein Kinases/metabolism ; THP-1 Cells ; Gene Knockdown Techniques ; Signal Transduction ; RNA, Small Interfering/genetics
Chemical Substances	GTP-Binding Proteins (EC 3.6.1.-) ; Lipopolysaccharides ; Cytokines ; GBP1 protein, human ; STAT1 Transcription Factor ; Chemokines ; Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; RNA, Small Interfering
Language	English
Publishing date	2024-03-10
Publishing country	Australia
Document type	Journal Article
ZDB-ID	224792-6
ISSN	1348-0421 ; 0385-5600
ISSN (online)	1348-0421
ISSN	0385-5600
DOI	10.1111/1348-0421.13123
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Article: [The influence of protein kinases ERK, JNK and nuclear transcriptional factor c-JUN on corticotropin signal transduction in adrenocortical cells].

Tron'ko, M D / Kovzun, O I / Mykosha, O S

Ukrains'kyi biokhimichnyi zhurnal (1999 )

2008 Volume 80, Issue 3, Page(s) 65–69

Abstract: ... I h after and was decreased 6 h after the injection. However, the level of p38 kinase was not changed ... c-Jun and c-Fos transcription factors in the adrenal cortex of male rats was studied. It was shown ... and continued decreasing with the increase of time after the injection. The level of c-Fos factor ...

Abstract	The estradiol effect on the expression level of ERK1/2, JNK, p38 mitogen-activated protein kinases, c-Jun and c-Fos transcription factors in the adrenal cortex of male rats was studied. It was shown that a single corticotropin injection caused significant changes of the ERK1/2 protein kinases levels in the adrenal cortex. This index was 1.6 times higher 1 h after the injection and was decreased 6 h after the injection. The corticotropin influence on JNK level is very significant. The protein kinase JNK level was 2.4-fold increased I h after and was decreased 6 h after the injection. However, the level of p38 kinase was not changed in these conditions. The level of c-Jun transcriptional factor increased 1.7 times 1 h after corticotropin treatment and continued decreasing with the increase of time after the injection. The level of c-Fos factor increased 1.7 times only 6 h after the injection. These changes may be an important factor of activation of adrenocortical function provoked by corticotropin.
MeSH term(s)	Adrenal Cortex/cytology ; Adrenal Cortex/drug effects ; Adrenal Cortex/enzymology ; Adrenocorticotropic Hormone/metabolism ; Adrenocorticotropic Hormone/pharmacology ; Animals ; Extracellular Signal-Regulated MAP Kinases/biosynthesis ; JNK Mitogen-Activated Protein Kinases/biosynthesis ; Male ; Proto-Oncogene Proteins c-fos/biosynthesis ; Proto-Oncogene Proteins c-jun/biosynthesis ; Rats ; Rats, Wistar ; Signal Transduction ; Time Factors ; p38 Mitogen-Activated Protein Kinases/biosynthesis
Chemical Substances	Proto-Oncogene Proteins c-fos ; Proto-Oncogene Proteins c-jun ; Adrenocorticotropic Hormone (9002-60-2) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; JNK Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Language	Ukrainian
Publishing date	2008-05
Publishing country	Ukraine
Document type	English Abstract ; Journal Article
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Article ; Online: Scaffold protein RACK1 regulates BR signaling by modulating the nuclear localization of BZR1.

Li, Zhiyong / Fu, Yajuan / Wang, Yuzhu / Liang, Jiansheng

The New phytologist

2023 Volume 239, Issue 5, Page(s) 1804–1818

Abstract: ... In this study, we show that the scaffold protein Receptor for Activated C Kinase 1 (RACK1) from Arabidopsis is ... retained in the cytosol by the conserved scaffold protein 14-3-3s. RACK1 can interact with BZR1 and ... Our study uncovers a new mechanism that integrates two kinds of conserved scaffold proteins (RACK1 and 14-3 ...

Abstract	Brassinosteroids (BRs) are a group of plant-specific steroid hormones, which induces the rapid nuclear localization of the positive transcriptional factors BRASSINAZOLE RESISTANT1/2 (BZR1/2). However, the mechanisms underlying the regulation of nucleocytoplasmic shuttling of BZR1 remain to be fully elucidated. In this study, we show that the scaffold protein Receptor for Activated C Kinase 1 (RACK1) from Arabidopsis is involved in BR signaling cascades through mediating the nuclear localization of BZR1, which is tightly retained in the cytosol by the conserved scaffold protein 14-3-3s. RACK1 can interact with BZR1 and competitively decrease the 14-3-3 interaction with BZR1 in cytosol, which efficiently enhances the nuclear localization of BZR1. 14-3-3 also retains RACK1 in cytosol through their interaction. Conversely, BR treatment enhances the nuclear localization of BZR1 by disrupting the 14-3-3 interaction with RACK1 and BZR1. Our study uncovers a new mechanism that integrates two kinds of conserved scaffold proteins (RACK1 and 14-3-3) coordinating BR signaling event.
MeSH term(s)	Arabidopsis Proteins/metabolism ; DNA-Binding Proteins/metabolism ; Arabidopsis/metabolism ; Cell Nucleus/metabolism ; Signal Transduction ; Plant Growth Regulators/metabolism ; Brassinosteroids/metabolism ; Phytosterols/metabolism ; Gene Expression Regulation, Plant ; Receptors for Activated C Kinase/metabolism
Chemical Substances	Arabidopsis Proteins ; DNA-Binding Proteins ; Plant Growth Regulators ; Brassinosteroids ; Phytosterols ; BZR1 protein, Arabidopsis ; RACK1 protein, Arabidopsis ; Receptors for Activated C Kinase
Language	English
Publishing date	2023-06-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208885-x
ISSN	1469-8137 ; 0028-646X
ISSN (online)	1469-8137
ISSN	0028-646X
DOI	10.1111/nph.19049
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Article ; Online: Klotho protein inhibits H

Cui, Wei / Leng, Bin / Wang, GaoPin

Canadian journal of physiology and pharmacology

2018 Volume 97, Issue 5, Page(s) 370–376

Abstract: Klotho protein secreted in the blood could act as a hormone to regulate various target organs and ... had antioxidative stress, anti-inflammatory, and antiapoptotic effects on vascular endothelial cells ... have a protective effect on the cardiovascular system. Numerous studies had shown that Klotho protein ...

Abstract	Klotho protein secreted in the blood could act as a hormone to regulate various target organs and have a protective effect on the cardiovascular system. Numerous studies had shown that Klotho protein had antioxidative stress, anti-inflammatory, and antiapoptotic effects on vascular endothelial cells. The purpose of this study was to investigate the protective mechanism of Klotho protein on oxidative damage of vascular endothelial cells induced by H
MeSH term(s)	Active Transport, Cell Nucleus/drug effects ; Antioxidants/metabolism ; Apoptosis/drug effects ; Cell Nucleus/drug effects ; Cell Nucleus/metabolism ; Cytoprotection/drug effects ; Gene Expression Regulation/drug effects ; Glucuronidase/metabolism ; Heme Oxygenase-1/metabolism ; Human Umbilical Vein Endothelial Cells/cytology ; Human Umbilical Vein Endothelial Cells/drug effects ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; Hydrogen Peroxide/pharmacology ; L-Lactate Dehydrogenase/metabolism ; Malondialdehyde/metabolism ; NF-E2-Related Factor 2/metabolism ; Oxidative Stress/drug effects ; Phosphatidylinositol 3-Kinase/metabolism ; Phosphorylation/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/drug effects ; Superoxide Dismutase/metabolism
Chemical Substances	Antioxidants ; NF-E2-Related Factor 2 ; Malondialdehyde (4Y8F71G49Q) ; Hydrogen Peroxide (BBX060AN9V) ; L-Lactate Dehydrogenase (EC 1.1.1.27) ; Heme Oxygenase-1 (EC 1.14.14.18) ; Superoxide Dismutase (EC 1.15.1.1) ; Phosphatidylinositol 3-Kinase (EC 2.7.1.137) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Glucuronidase (EC 3.2.1.31) ; klotho protein (EC 3.2.1.31)
Language	English
Publishing date	2018-12-21
Publishing country	Canada
Document type	Journal Article
ZDB-ID	127527-6
ISSN	1205-7541 ; 0008-4212
ISSN (online)	1205-7541
ISSN	0008-4212
DOI	10.1139/cjpp-2018-0277
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Zs.A 589: Show issues

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Article ; Online: Mammalian reovirus µ1 protein attenuates RIG-I and MDA5-mediated signaling transduction by blocking IRF3 phosphorylation and nuclear translocation.

Wu, Bei / Li, Dianyu / Bai, Huisheng / Mo, Rongqian / Li, Hongshan / Xie, Jingying / Zhang, Xiangbo / Yang, Yanmei / Li, Huixia / Idris, Adi / Li, Xiangrong / Feng, Ruofei

Molecular immunology

2024 Volume 170, Page(s) 131–143

Abstract: ... and attenuated RIG-I/MDA5-mediated signaling axis transduction during MRV infection. Importantly ... capsid protein μ1 is a key factor in antagonizing RLRs signaling cascades and provide new strategies ... the proteasomal and lysosomal pathways. Additionally, we show that μ1 protein can physically interact with MDA5 ...

Abstract	Mammalian reovirus (MRV) is a non-enveloped, gene segmented double-stranded RNA (dsRNA) virus. It is an important zoonotic pathogen that infects many mammals and vertebrates that act as natural hosts and causes respiratory and digestive tract diseases. Studies have reported that RIG-I and MDA5 in the innate immune cytoplasmic RNA-sensing RIG-like receptor (RLR) signaling pathway can recognize dsRNA from MRV and promote antiviral type I interferon (IFN) responses. However, the mechanism by which many MRV-encoded proteins evade the host innate immune response remains unclear. Here, we show that exogenous μ1 protein promoted the proliferation of MRV in vitro, while knockdown of MRV μ1 protein expression by shRNA could impair MRV proliferation. Specifically, μ1 protein inhibited MRV or poly(I:C)-induced IFN-β expression, and attenuated RIG-I/MDA5-mediated signaling axis transduction during MRV infection. Importantly, we found that μ1 protein significantly decreased IFN-β mRNA expression induced by MDA5, RIG-I, MAVS, TBK1, IRF3(5D), and degraded the protein expression of exogenous MDA5, RIG-I, MAVS, TBK1 and IRF3 via the proteasomal and lysosomal pathways. Additionally, we show that μ1 protein can physically interact with MDA5, RIG-I, MAVS, TBK1, and IRF3 and attenuate the RIG-I/MDA5-mediated signaling cascades by blocking the phosphorylation and nuclear translocation of IRF3. In conclusion, our findings reveal that MRV outer capsid protein μ1 is a key factor in antagonizing RLRs signaling cascades and provide new strategies for effective prevention and treatment of MRV infection.
MeSH term(s)	Interferon-Induced Helicase, IFIH1/metabolism ; Interferon-Induced Helicase, IFIH1/genetics ; Interferon Regulatory Factor-3/metabolism ; DEAD Box Protein 58/metabolism ; Signal Transduction/immunology ; Humans ; Phosphorylation ; Receptors, Immunologic ; Orthoreovirus, Mammalian/immunology ; Orthoreovirus, Mammalian/physiology ; HEK293 Cells ; Interferon-beta/metabolism ; Interferon-beta/immunology ; Animals ; Cell Nucleus/metabolism ; Reoviridae Infections/immunology ; Viral Proteins/metabolism ; Active Transport, Cell Nucleus ; Immunity, Innate/immunology ; Protein Serine-Threonine Kinases
Chemical Substances	Interferon-Induced Helicase, IFIH1 (EC 3.6.4.13) ; Interferon Regulatory Factor-3 ; DEAD Box Protein 58 (EC 3.6.4.13) ; Receptors, Immunologic ; RIGI protein, human (EC 3.6.1.-) ; IFIH1 protein, human (EC 3.6.1.-) ; IRF3 protein, human ; Interferon-beta (77238-31-4) ; Viral Proteins ; TBK1 protein, human (EC 2.7.11.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2024-04-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/j.molimm.2024.04.010
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Article ; Online: PDCD4 restricts PRRSV replication in an eIF4A-dependent manner and is antagonized by the viral nonstructural protein 9.

Wei, Ruiping / Zhang, Xiaoxiao / Wang, Xiaoying / Li, Lu / Fu, Yajie / Chen, Yaosheng / Liu, Xiaohong / Guo, Chunhe

Journal of virology

2024 Volume 98, Issue 5, Page(s) e0006024

Abstract: ... of programmed cell death 4 (PDCD4) were strongly downregulated by PRRSV and significantly rescued by MG132. Further ... to the cytoplasm, and the viral nonstructural protein 9 (Nsp9) promoted PDCD4 proteasomal degradation ... by porcine reproductive and respiratory syndrome virus (PRRSV), we conducted a quantitative proteomics screen of PRRSV-infected Marc-145 cells under ...

Abstract	As obligate parasites, viruses have evolved multiple strategies to evade the host immune defense. Manipulation of the host proteasome system to degrade specific detrimental factors is a common viral countermeasure. To identify host proteins targeted for proteasomal degradation by porcine reproductive and respiratory syndrome virus (PRRSV), we conducted a quantitative proteomics screen of PRRSV-infected Marc-145 cells under the treatment with proteasome inhibitor MG132. The data revealed that the expression levels of programmed cell death 4 (PDCD4) were strongly downregulated by PRRSV and significantly rescued by MG132. Further investigation confirmed that PRRSV infection induced the translocation of PDCD4 from the nucleus to the cytoplasm, and the viral nonstructural protein 9 (Nsp9) promoted PDCD4 proteasomal degradation in the cytoplasm by activating the Akt-mTOR-S6K1 pathway. The C-terminal domain of Nsp9 was responsible for PDCD4 degradation. As for the role of PDCD4 during PRRSV infection, we demonstrated that PDCD4 knockdown favored viral replication, while its overexpression significantly attenuated replication, suggesting that PDCD4 acts as a restriction factor for PRRSV. Mechanistically, we discovered eukaryotic translation initiation factor 4A (eIF4A) was required for PRRSV. PDCD4 interacted with eIF4A through four sites (E249, D253, D414, and D418) within its two MA3 domains, disrupting eIF4A-mediated translation initiation in the 5'-untranslated region of PRRSV, thereby inhibiting PRRSV infection. Together, our study reveals the antiviral function of PDCD4 and the viral strategy to antagonize PDCD4. These results will contribute to our understanding of the immune evasion strategies employed by PRRSV and offer valuable insights for developing new antiviral targets.IMPORTANCEPorcine reproductive and respiratory syndrome virus (PRRSV) infection results in major economic losses in the global swine industry and is difficult to control effectively. Here, using a quantitative proteomics screen, we identified programmed cell death 4 (PDCD4) as a host protein targeted for proteasomal degradation by PRRSV. We demonstrated that PDCD4 restricts PRRSV replication by interacting with eukaryotic translation initiation factor 4A, which is required for translation initiation in the viral 5'-untranslated region. Additionally, four sites within two MA3 domains of PDCD4 are identified to be responsible for its antiviral function. Conversely, PRRSV nonstructural protein 9 promotes PDCD4 proteasomal degradation in the cytoplasm by activating the Akt-mTOR-S6K1 pathway, thus weakening the anti-PRRSV function. Our work unveils PDCD4 as a previously unrecognized host restriction factor for PRRSV and reveals that PRRSV develops countermeasures to overcome PDCD4. This will provide new insights into virus-host interactions and the development of new antiviral targets.
MeSH term(s)	Porcine respiratory and reproductive syndrome virus/physiology ; Animals ; Viral Nonstructural Proteins/metabolism ; Viral Nonstructural Proteins/genetics ; Virus Replication ; Eukaryotic Initiation Factor-4A/metabolism ; Eukaryotic Initiation Factor-4A/genetics ; Apoptosis Regulatory Proteins/metabolism ; Apoptosis Regulatory Proteins/genetics ; Swine ; Cell Line ; RNA-Binding Proteins/metabolism ; RNA-Binding Proteins/genetics ; Proteasome Endopeptidase Complex/metabolism ; Host-Pathogen Interactions ; Proteolysis ; Humans ; Porcine Reproductive and Respiratory Syndrome/metabolism ; Porcine Reproductive and Respiratory Syndrome/virology ; TOR Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction
Language	English
Publishing date	2024-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.00060-24
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Article ; Online: Classical swine fever virus NS5A protein antagonizes innate immune response by inhibiting the NF-κB signaling.

Sun, Jinfu / Li, Jiaying / Li, Liming / Yu, Haixiao / Ma, Ping / Wang, Yingnan / Zhu, Jinqi / Feng, Zezhong / Tu, Changchun

Virologica Sinica

2023 Volume 38, Issue 6, Page(s) 900–910

Abstract: ... involved in viral genomic replication, protein translation, assembly of infectious virus particles, and ... NF-κB) signaling induced by poly(I:C); however, the mechanism involved has not been elucidated. Here ... of the IκB kinase (IKK) complex, to inhibit the NF-κB signaling pathway. Further investigations showed ...

Abstract	The NS5A non-structural protein of classical swine fever virus (CSFV) is a multifunctional protein involved in viral genomic replication, protein translation, assembly of infectious virus particles, and regulation of cellular signaling pathways. Previous report showed that NS5A inhibited nuclear factor kappa B (NF-κB) signaling induced by poly(I:C); however, the mechanism involved has not been elucidated. Here, we reported that NS5A directly interacted with NF-κB essential modulator (NEMO), a regulatory subunit of the IκB kinase (IKK) complex, to inhibit the NF-κB signaling pathway. Further investigations showed that the zinc finger domain of NEMO and the aa 126-250 segment of NS5A are essential for the interaction between NEMO and NS5A. Mechanistic analysis revealed that NS5A mediated the proteasomal degradation of NEMO. Ubiquitination assay showed that NS5A induced the K27-linked but not the K48-linked polyubiquitination of NEMO for proteasomal degradation. In addition, NS5A blocked the K63-linked polyubiquitination of NEMO, thus inhibiting IKK phosphorylation, IκBα degradation, and NF-κB activation. These findings revealed a novel mechanism by which CSFV inhibits host innate immunity, which might guide the drug design against CSFV in the future.
MeSH term(s)	Animals ; Swine ; NF-kappa B/metabolism ; Classical Swine Fever Virus/metabolism ; Signal Transduction ; I-kappa B Kinase/genetics ; I-kappa B Kinase/metabolism ; Immunity, Innate
Chemical Substances	NF-kappa B ; I-kappa B Kinase (EC 2.7.11.10)
Language	English
Publishing date	2023-09-14
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1011219-4
ISSN	1995-820X ; 1000-3223 ; 1003-5125
ISSN (online)	1995-820X
ISSN	1000-3223 ; 1003-5125
DOI	10.1016/j.virs.2023.09.002
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Article ; Online: LDL Affects the Immunomodulatory Response of Endothelial Cells by Modulation of the Promyelocytic Leukemia Protein (PML) Expression via PKC.

Roos, Kerrin / Berkholz, Janine

International journal of molecular sciences

2023 Volume 24, Issue 8

Abstract: ... HUVECs and EA.hy926 cells). RT-qPCR, immunoblotting, and immunofluorescence analyses showed that LDL ... but not HDL induced higher PML expression and higher numbers of PML-nuclear bodies (PML-NBs). Transfection ... in ECs are realized are not fully understood. Since promyelocytic leukemia protein (PML) plays a role ...

Abstract	In addition to its function as an intravascular lipid transporter, LDL also triggers signal transduction in endothelial cells (ECs), which, among other things, trigger immunomodulatory cascades, e.g., IL-6 upregulation. However, the molecular mechanisms of how these LDL-triggered immunological responses in ECs are realized are not fully understood. Since promyelocytic leukemia protein (PML) plays a role in promoting inflammatory processes, we examined the relationship between LDL, PML, and IL-6 in human ECs (HUVECs and EA.hy926 cells). RT-qPCR, immunoblotting, and immunofluorescence analyses showed that LDL but not HDL induced higher PML expression and higher numbers of PML-nuclear bodies (PML-NBs). Transfection of the ECs with a
MeSH term(s)	Humans ; Endothelial Cells/metabolism ; Interleukin-6/genetics ; Interleukin-8 ; Nuclear Proteins/genetics ; Promyelocytic Leukemia Protein/genetics ; Promyelocytic Leukemia Protein/metabolism ; Transcription Factors/metabolism ; Lipoproteins, LDL/metabolism ; Protein Kinase C/metabolism
Chemical Substances	Interleukin-6 ; Interleukin-8 ; Nuclear Proteins ; Promyelocytic Leukemia Protein ; Transcription Factors ; Lipoproteins, LDL ; Protein Kinase C (EC 2.7.11.13)
Language	English
Publishing date	2023-04-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24087306
Database	MEDical Literature Analysis and Retrieval System OnLINE

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