{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T07:01:28Z","timestamp":1781334088666,"version":"3.54.1"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>DNA-PK (DNA-dependent protein kinase) is a stress-activated serine\/threonine kinase that plays a central role in vascular smooth muscle cell proliferation and vascular proliferative disease processes such as neointimal formation. In this study, we link the activation of DNA-PK to the function of the transcription factor YB-1 (Y-box binding protein).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>To identify YB-1 phosphorylation by DNA-PK, we generated different YB-1-expressing vectors. YB-1 nuclear translocation was investigated using immunoblotting and immunofluorescence staining. For YB-1 activity, luciferase assays were performed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>We show by mutational analysis and kinase assay that the transcriptional regulator YB-1 is a substrate of DNA-PK. Blockade of DNA-PK by specific inhibitors revealed its critical involvement in YB-1phosphorylation as demonstrated by inhibition of an overexpressed YB-1 reporter construct. Using DNA-PK-deficient cells, we demonstrate that the shuttling of YB-1 from the cytoplasm to the nucleus is dependent on DNA-PK and that the N-terminal domain of YB-1 is phosphorylated at threonine 89. Point mutation of YB-1 at this residue abrogated the translocation of YB-1 into the nucleus. The phosphorylation of YB-1 by DNA-PK increased cellular DNA repair after exposure to ionizing radiation. Atherosclerotic tissue specimens were analyzed by immunohistochemistry. The DNA-PK subunits and YB-1 phosphorylated at T89 were found colocalized suggesting their in vivo interaction. In mice, the local application of the specific DNA-PK inhibitor NU7026 via thermosensitive Pluronic F-127 gel around dilated arteries significantly reduced the phosphorylation of YB-1.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>DNA-PK directly phosphorylates YB-1 and, this way, modulates YB-1 function. This interaction could be demonstrated in vivo, and colocalization in human atherosclerotic plaques suggests clinical relevance of our finding. Phosphorylation of YB-1 by DNA-PK may represent a novel mechanism governing atherosclerotic plaque progression.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.122.317922","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T10:00:41Z","timestamp":1670493641000},"page":"300-311","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["DNA-Dependent Protein Kinase Mediates YB-1 (Y-Box Binding Protein)-Induced Double Strand Break Repair"],"prefix":"10.1161","volume":"43","author":[{"given":"Till","family":"N\u00f6then","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiology and Angiology (T.N., M.A.S., S.W., R.C.B.-D., S.M.), Otto-von-Guericke University, Magdeburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4042-6474","authenticated-orcid":true,"given":"Mohsen Abdi","family":"Sarabi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiology and Angiology (T.N., M.A.S., S.W., R.C.B.-D., S.M.), Otto-von-Guericke University, Magdeburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7201-0836","authenticated-orcid":true,"given":"S\u00f6nke","family":"Weinert","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiology and Angiology (T.N., M.A.S., S.W., R.C.B.-D., S.M.), Otto-von-Guericke University, Magdeburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9845-6393","authenticated-orcid":true,"given":"Werner","family":"Zuschratter","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Neurobiology, Magdeburg, Germany (W.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronnie","family":"Morgenroth","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Hypertension, Diabetes and Endocrinology (R.M., P.R.M.), Otto-von-Guericke University, Magdeburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Mertens","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology and Hypertension, Diabetes and Endocrinology (R.M., P.R.M.), Otto-von-Guericke University, Magdeburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruediger C.","family":"Braun-Dullaeus","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiology and Angiology (T.N., M.A.S., S.W., R.C.B.-D., S.M.), Otto-von-Guericke University, Magdeburg, 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