{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:23:52Z","timestamp":1790180632259,"version":"4.1.0"},"reference-count":67,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T00:00:00Z","timestamp":1650499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/19\/37\/34438"],"award-info":[{"award-number":["FS\/19\/37\/34438"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The second messenger, cAMP has potent immunosuppressive and anti-inflammatory actions. These have been attributed, in part, to the ability of cAMP-induced signals to interfere with the function of the proinflammatory transcription factor Nuclear Factor-kappa B (NF-\u03baB). However, the mechanisms underlying the modulation of NF-\u03baB activity by cAMP remain unclear. Here we demonstrate an important role for cAMP-mediated increase in nuclear actin monomer levels in inhibiting NF-\u03baB activity. Elevated cAMP or forced expression of a nuclear localised polymerisation defective actin mutant (NLS-ActinR62D) inhibited basal and TNF\u03b1 induced mRNA levels of NF-\u03baB-dependent genes and NF-\u03baB-dependent reporter gene activity. Elevated cAMP or NLS-ActinR62D did not affect NF-\u03baB nuclear translocation but did reduce total cellular and nuclear RelA\/p65 levels. Preventing the cAMP-induced increase in nuclear actin monomer, either by expressing a nuclear localised active mutant of the actin polymerising protein mDIA, silencing components of the nuclear actin import complex IPO9 and CFL1 or overexpressing the nuclear export complex XPO6, rescued RelA\/p65 levels and NF-\u03baB reporter gene activity in forskolin-stimulated cells. Elevated cAMP or NLS-ActinR62D reduced the half-life of RelA\/p65, which was reversed by the proteasome inhibitor MG132. Accordingly, forskolin stimulated association of RelA\/p65 with ubiquitin affinity beads, indicating increased ubiquitination of RelA\/p65 or associated proteins. Taken together, our data demonstrate a novel mechanism underlying the anti-inflammatory effects of cAMP and highlight the important role played by nuclear actin in the regulation of inflammation.<\/jats:p>","DOI":"10.3390\/cells11091414","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T05:07:22Z","timestamp":1650604042000},"page":"1414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cyclic-AMP Increases Nuclear Actin Monomer Which Promotes Proteasomal Degradation of RelA\/p65 Leading to Anti-Inflammatory Effects"],"prefix":"10.3390","volume":"11","author":[{"given":"Joseph W.","family":"Hawkins","sequence":"first","affiliation":[{"name":"School of Translational Health Sciences, Faculty of Health Sciences, University of Bristol, Research Floor Level 7, Bristol Royal Infirmary, Bristol BS2 8HW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine C.","family":"McNeill","sequence":"additional","affiliation":[{"name":"School of Translational Health Sciences, Faculty of Health Sciences, University of Bristol, Research Floor Level 7, Bristol Royal Infirmary, Bristol BS2 8HW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Ebrahimighaei","sequence":"additional","affiliation":[{"name":"School of Translational Health Sciences, Faculty of Health Sciences, University of Bristol, Research Floor Level 7, Bristol Royal Infirmary, Bristol BS2 8HW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3894-0623","authenticated-orcid":false,"given":"Harry H.","family":"Mellor","sequence":"additional","affiliation":[{"name":"School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5559-9204","authenticated-orcid":false,"given":"Andrew C.","family":"Newby","sequence":"additional","affiliation":[{"name":"School of Translational Health Sciences, Faculty of Health Sciences, University of Bristol, Research Floor Level 7, Bristol Royal Infirmary, Bristol BS2 8HW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Bond","sequence":"additional","affiliation":[{"name":"School of Translational Health Sciences, Faculty of Health Sciences, University of Bristol, Research Floor Level 7, Bristol Royal Infirmary, Bristol BS2 8HW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1161\/CIRCULATIONAHA.105.537878","article-title":"Pathophysiology of coronary artery disease","volume":"111","author":"Libby","year":"2005","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1253\/circj.CJ-18-0063","article-title":"Inflammatory Mechanisms of Cardiovascular Remodeling","volume":"82","author":"Anzai","year":"2018","journal-title":"Circ. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3389\/fcvm.2018.00003","article-title":"Inflammation in Vein Graft Disease","volume":"5","author":"Quax","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1161\/01.ATV.0000037100.44766.5B","article-title":"Inflammation and Restenosis in the Stent Era","volume":"22","author":"Welt","year":"2002","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/S0008-6363(01)00220-6","article-title":"Inhibition of transcription factor NF-kappa B reduces matrix metalloproteinase-1,-3 and-9 production by vascular smooth muscle cells","volume":"50","author":"Bond","year":"2001","journal-title":"Cardiovasc. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0014-5793(98)01034-5","article-title":"Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines: An absolute requirement for transcription factor NF-kappa B","volume":"435","author":"Bond","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1161\/ATVBAHA.114.305218","article-title":"Myocardin Regulates Vascular Smooth Muscle Cell Inflammatory Activation and Disease","volume":"35","author":"Talasila","year":"2015","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5483\/BMBRep.2014.47.1.285","article-title":"Role of vascular smooth muscle cell in the inflammation of atherosclerosis","volume":"47","author":"Lim","year":"2014","journal-title":"BMB Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1152\/physiolgenomics.00160.2011","article-title":"Interleukin-1\u03b2 modulates smooth muscle cell phenotype to a distinct inflammatory state relative to PDGF-DD via NF-\u03baB-dependent mechanisms","volume":"44","author":"Alexander","year":"2012","journal-title":"Physiol. Genom."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1159\/000250095","article-title":"Complex Regulation and Function of the Inflammatory Smooth Muscle Cell Phenotype in Atherosclerosis","volume":"47","author":"Orr","year":"2010","journal-title":"J. Vasc. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1093\/cvr\/cvs115","article-title":"Smooth muscle cell phenotypic switching in atherosclerosis","volume":"95","author":"Gomez","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/0306-9877(81)90084-0","article-title":"Smooth muscle phenotypic modulation: Role in atherogenesis","volume":"7","author":"Campbell","year":"1981","journal-title":"Med. Hypotheses"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1161\/ATVBAHA.109.184382","article-title":"Human IL-8 Regulates Smooth Muscle Cell VCAM-1 Expression in Response to Endothelial Cells Exposed to Atheroprone Flow","volume":"29","author":"Hastings","year":"2009","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_14","first-page":"1085","article-title":"Activation of the NF-kappa B and I kappa B system in smooth muscle cells after rat arterial injury. Induction of vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1","volume":"151","author":"Landry","year":"1997","journal-title":"Am. J. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1093\/cvr\/cvv130","article-title":"Cytosolic Hsp60 orchestrates the survival and inflammatory responses of vascular smooth muscle cells in injured aortic vessels","volume":"106","author":"Choi","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1016\/j.ajpath.2013.01.022","article-title":"Peptide Inhibitor of NF-\u03baB Translocation Ameliorates Experimental Atherosclerosis","volume":"182","author":"Mallavia","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.1161\/01.CIR.103.25.3117","article-title":"Differential expression of matrix metalloproteinases after stent implantation and balloon angioplasty in the hypercholesterolemic rabbit","volume":"103","author":"Feldman","year":"2001","journal-title":"Circulation"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cell.2016.12.012","article-title":"30 Years of NF-\u03baB: A Blossoming of Relevance to Human Pathobiology","volume":"168","author":"Zhang","year":"2017","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1126\/science.3140380","article-title":"IkB: A specific Inhibitor of the NF-kB transcription factor","volume":"242","author":"Baeuerle","year":"1988","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1242\/jcs.182097","article-title":"Oxidized LDL induces FAK-dependent RSK signaling to drive NF-\u03baB activation and VCAM-1 expression","volume":"129","author":"Yurdagul","year":"2016","journal-title":"J. Cell Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1089\/wound.2017.0735","article-title":"TLR4 Ligands Selectively Synergize to Induce Expression of IL-8","volume":"6","author":"Valenty","year":"2017","journal-title":"Adv. Wound Care"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"30765","DOI":"10.1016\/S0021-9258(18)47345-0","article-title":"Fibronectin attachment activates the NF-kappa-B p50\/p65 hetterodimer in fibroblasts and smooth-muscle cells","volume":"269","author":"Qwarnstrom","year":"1994","journal-title":"Int. J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.1007\/s00018-011-0757-8","article-title":"Cyclic AMP: A selective modulator of NF-\u03baB action","volume":"68","author":"Gerlo","year":"2011","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"20828","DOI":"10.1074\/jbc.271.34.20828","article-title":"Elevated Cyclic AMP Inhibits NF-\u03baB-mediated Transcription in Human Monocytic Cells and Endothelial Cells","volume":"271","author":"Ollivier","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"503","DOI":"10.5551\/jat.3392","article-title":"Anti-inflammatory role of cilostazol in vascular smooth muscle cells in vitro and in vivo","volume":"17","author":"Aoki","year":"2010","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1161\/01.RES.0000091074.33584.F0","article-title":"Role of Phosphodiesterase 3 in NO\/cGMP-Mediated Antiinflammatory Effects in Vascular Smooth Muscle Cells","volume":"93","author":"Aizawa","year":"2003","journal-title":"Circ. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/jlb.63.1.101","article-title":"Anti-inflammatory activities of cAMP-elevating agents: Enhancement of IL-10 synthesis and concurrent suppression of TNF production","volume":"63","author":"Eigler","year":"1998","journal-title":"J. Leukocyte Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1002\/j.1460-2075.1995.tb07191.x","article-title":"RelA\/p65 is a molecular target for the immunosuppressive action of protein kinase A","volume":"14","author":"Neumann","year":"1995","journal-title":"EMBO J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/S0092-8674(00)80222-6","article-title":"The Transcriptional Activity of NF-\u03baB Is Regulated by the I\u03baB-Associated PKAc Subunit through a Cyclic AMP\u2013Independent Mechanism","volume":"89","author":"Zhong","year":"1997","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1093\/cvr\/cvn188","article-title":"Rho GTPase, Rac1, regulates Skp2 levels, vascular smooth muscle cell proliferation, and intima formation in vitro and in vivo","volume":"80","author":"Bond","year":"2008","journal-title":"Cardiovasc. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.yjmcc.2010.10.010","article-title":"PKA and Epac synergistically inhibit smooth muscle cell proliferation","volume":"50","author":"Hewer","year":"2011","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.yjmcc.2014.02.001","article-title":"Inhibition of Egr1 expression underlies the anti-mitogenic effects of cAMP in vascular smooth muscle cells","volume":"72","author":"Kimura","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yjmcc.2015.11.024","article-title":"The Hippo pathway mediates inhibition of vascular smooth muscle cell proliferation by cAMP","volume":"90","author":"Kimura","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3681","DOI":"10.1038\/s41598-017-03337-0","article-title":"Divergent Regulation of Actin Dynamics and Megakaryoblastic Leukemia-1 and -2 (Mkl1\/2) by cAMP in Endothelial and Smooth Muscle Cells","volume":"7","author":"Smith","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_35","first-page":"1005","article-title":"S-phase kinase-associated protein-2 regulates vascular smooth muscle cell migration via p21Cip1-Cdc42\/Rac1, but not p27Kip1-RhoA signalling","volume":"32","author":"Wu","year":"2011","journal-title":"Eur. Heart J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1126\/science.1141084","article-title":"Nuclear Actin Regulates Dynamic Subcellular Localization and Activity of the SRF Cofactor MAL","volume":"316","author":"Vartiainen","year":"2007","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"118691","DOI":"10.1016\/j.bbamcr.2020.118691","article-title":"Nuclear actin regulates cell proliferation and migration via inhibition of SRF and TEAD","volume":"1867","author":"McNeill","year":"2020","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1161\/01.RES.0000079027.44309.53","article-title":"Dismantling of Cadherin-Mediated Cell-Cell Contacts Modulates Smooth Muscle Cell Proliferation","volume":"92","author":"Uglow","year":"2003","journal-title":"Circ. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1126\/science.1235038","article-title":"Nuclear Actin Network Assembly by Formins Regulates the SRF Coactivator MAL","volume":"340","author":"Baarlink","year":"2013","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1677\/jme.0.0290023","article-title":"Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): Trends and problems","volume":"29","author":"Bustin","year":"2002","journal-title":"J. Mol. Endocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"E544","DOI":"10.1073\/pnas.1118880109","article-title":"Active maintenance of nuclear actin by importin 9 supports transcription","volume":"109","author":"Dopie","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5928","DOI":"10.1093\/emboj\/cdg565","article-title":"Exportin 6: A novel nuclear export receptor that is specific for profilin\u00b7actin complexes","volume":"22","author":"Hartmann","year":"2003","journal-title":"EMBO J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.coi.2012.12.005","article-title":"Regulation of NF-\u03baB by ubiquitination","volume":"25","author":"Chen","year":"2013","journal-title":"Curr. Opin. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Collins, P., Mitxitorena, I., and Carmody, R.J. (2016). The Ubiquitination of NF-\u03baB Subunits in the Control of Transcription. Cells, 5.","DOI":"10.3390\/cells5020023"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"14514","DOI":"10.1016\/S0021-9258(19)73332-8","article-title":"Degradation of proto-oncoprotein c-Rel by the ubiquitin-proteasome pathway","volume":"274","author":"Chen","year":"1999","journal-title":"Int. J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/onc.2011.253","article-title":"Regulation of NF-\u03baB activity by competition between RelA acetylation and ubiquitination","volume":"31","author":"Li","year":"2011","journal-title":"Oncogene"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1084\/jem.20040196","article-title":"Degradation of Promoter-bound p65\/RelA Is Essential for the Prompt Termination of the Nuclear Factor \u03baB Response","volume":"200","author":"Saccani","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1111\/j.1365-2249.1995.tb03123.x","article-title":"The role of cAMP regulation in controlling inflammation","volume":"101","author":"Moore","year":"1995","journal-title":"Clin. Exp. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1126\/science.184.4132.19","article-title":"Modulation of Inflammation and Immunity by Cyclic AMP","volume":"184","author":"Bourne","year":"1974","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/eji.200425524","article-title":"Adenosine and cAMP are potent inhibitors of the NF-?B pathway downstream of immunoreceptors","volume":"35","author":"Minguet","year":"2004","journal-title":"Eur. J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/j.1476-5381.2011.01808.x","article-title":"Regulation of the inflammatory response of vascular endothelial cells by EPAC1","volume":"166","author":"Parnell","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1016\/j.febslet.2014.02.038","article-title":"The role of c-Jun in controlling the EPAC1-dependent induction of the SOCS3 gene in HUVECs","volume":"588","author":"Wiejak","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3738","DOI":"10.1523\/JNEUROSCI.4439-07.2008","article-title":"Protein Kinase A-Induced Phosphorylation of the p65 Subunit of Nuclear Factor- B Promotes Schwann Cell Differentiation into a Myelinating Phenotype","volume":"28","author":"Yoon","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/S1097-2765(00)80066-0","article-title":"Phosphorylation of NF-\u03baB p65 by PKA Stimulates Transcriptional Activity by Promoting a Novel Bivalent Interaction with the Coactivator CBP\/p300","volume":"1","author":"Zhong","year":"1998","journal-title":"Mol. Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.jss.2008.12.018","article-title":"Cyclic AMP Inhibits IL-1\u03b2 Plus IFN\u03b3-Induced NF-\u03baB Translocation in Hepatocytes by a PKA Independent Mechanism","volume":"159","author":"Hong","year":"2010","journal-title":"J. Surg. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1084\/jem.179.3.931","article-title":"Interleukin 2 transcription factors as molecular targets of cAMP inhibition: Delayed inhibition kinetics and combinatorial transcription roles","volume":"179","author":"Chen","year":"1994","journal-title":"J. Exp. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"ra28","DOI":"10.1126\/scisignal.2000202","article-title":"Suppression of LPS-Induced TNF-\u03b1 Production in Macrophages by cAMP Is Mediated by PKA-AKAP95-p105","volume":"2","author":"Wall","year":"2009","journal-title":"Sci. Signal."},{"key":"ref_58","first-page":"212","article-title":"Familiarer, angeborener Morbus Welhofii?","volume":"68","author":"Wiskott","year":"1937","journal-title":"Monatsschr. Kinderheilkd"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1016\/j.bbamcr.2019.06.013","article-title":"Elevated cyclic-AMP represses expression of exchange protein activated by cAMP (EPAC1) by inhibiting YAP-TEAD activity and HDAC-mediated histone deacetylation","volume":"1866","author":"Ebrahimighaei","year":"2019","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Paco, S., Hummel, M., Pl\u00e1, V., Sumoy, L., and Aguado, F. (2016). Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes. BMC Genom., 17.","DOI":"10.1186\/s12864-016-2623-4"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/oxfordjournals.jbchem.a127789","article-title":"Extraction of a protein resembling actin from the cell nucleus of the calf thymus","volume":"54","author":"Ohnishi","year":"1963","journal-title":"J. Biochem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1002\/ar.23959","article-title":"Nuclear Actin: From Discovery to Function","volume":"301","author":"Kelpsch","year":"2018","journal-title":"Anat. Rec."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3335","DOI":"10.3389\/fimmu.2020.604206","article-title":"Actin Remodeling Defects Leading to Autoinflammation and Immune Dysregulation","volume":"11","author":"Papa","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1111\/imr.12114","article-title":"Actin cytoskeletal defects in immunodeficiency","volume":"256","author":"Moulding","year":"2013","journal-title":"Immunol. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1542\/peds.13.2.133","article-title":"Pedigree demonstrating a sex-linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea","volume":"13","author":"Aldrich","year":"1954","journal-title":"Pediatrics"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/nri884","article-title":"Wasp in immune-system organization and function","volume":"2","author":"Thrasher","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1007\/s00018-011-0912-2","article-title":"Monoubiquitination of nuclear RelA negatively regulates NF-\u03baB activity independent of proteasomal degradation","volume":"69","author":"Hochrainer","year":"2012","journal-title":"Cell. Mol. Life Sci."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/9\/1414\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:58:34Z","timestamp":1760137114000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/9\/1414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,21]]},"references-count":67,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["cells11091414"],"URL":"https:\/\/doi.org\/10.3390\/cells11091414","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,21]]}}}