{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:05:11Z","timestamp":1791223511051,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,3,19]],"date-time":"2009-03-19T00:00:00Z","timestamp":1237420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008321","name":"Pennsylvania State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2009,8]]},"abstract":"<jats:p>\n                    Controlling the HIV\/AIDS epidemic remains a major challenge, with approximately 5 million new HIV infections annually. Cyclopentenone prostaglandins (CyPG), such as 15\u2010deoxy\u2010\u25b3\n                    <jats:sup>1214<\/jats:sup>\n                    \u2010PGJ\n                    <jats:sub>2<\/jats:sub>\n                    (15d\u2010PGJ\n                    <jats:sub>2<\/jats:sub>\n                    ), are arachidonic acid\u2010derived endogenous electrophiles that possess anti\u2010HIV activity by an unknown mechanism. Given that the reactive \u03b1,\u03b2\u2010unsaturated ketone in the cyclopentenone ring of 15d\u2010PGJ\n                    <jats:sub>2<\/jats:sub>\n                    covalently modifies key Cys thiols in select proteins, we hypothesized that 15d\u2010PGJ\n                    <jats:sub>2<\/jats:sub>\n                    inhibits HIV transcription and replication by targeting Cys thiols in HIV\u20101 Tat. Tat is a potent transactivator of viral gene expression required for HIV transcriptional elongation and replication. Our studies indicate that 15d\u2010PGJ\n                    <jats:sub>2<\/jats:sub>\n                    treatment of cells inhibits Tat\u2010dependent transcription and replication of HIV\u20101, while 9,10\u2010dihydro\u201015d\u2010PGJ\n                    <jats:sub>2<\/jats:sub>\n                    , PGE\n                    <jats:sub>2<\/jats:sub>\n                    , PGF\n                    <jats:sub>2\u03b1<\/jats:sub>\n                    , or PGD\n                    <jats:sub>2<\/jats:sub>\n                    that lack the reactive \u03b1,\u03b2\u2010unsaturated ketone were ineffective. The inhibition of Tat activity by 15d\u2010PGJ\n                    <jats:sub>2<\/jats:sub>\n                    was dose\u2010dependent, with an IC\n                    <jats:sub>50<\/jats:sub>\n                    of 1.2 \u03b2M and independent of NF\u2010\u03baB pathway. Furthermore, using a biotinylated derivative of 15d\u2010PGJ\n                    <jats:sub>2<\/jats:sub>\n                    , we demonstrate that 15d\u2010PGJ\n                    <jats:sub>2<\/jats:sub>\n                    modifies free Cys\u2010thiols in Tat to form covalent Michael adducts and that the interaction was further increased on reduction of Tat. 15d\u2010PGJ\n                    <jats:sub>2<\/jats:sub>\n                    \u2010 modified Tat was unable to transactivate the HIV long terminal repeat in U937 human macrophages. These data demonstrate that Tat acts as a molecular target of CyPG leading to the inhibition of transcription and also suggest a novel therapeutic approach to complement current antiretroviral strategies for HIV\/AIDS.\u2014 Kalantari, P.,Narayan, V., Henderson, A. J., Prabhu, K. S. 15\u2010Deoxy\u2010A12,14\u2010prostaglandin J2 inhibits HIV\u20101 transactivating protein, Tat, through covalent modification. FASEBJ. 23, 2366\u20132373 (2009)\n                  <\/jats:p>","DOI":"10.1096\/fj.08-124982","type":"journal-article","created":{"date-parts":[[2009,3,19]],"date-time":"2009-03-19T20:40:24Z","timestamp":1237495224000},"page":"2366-2373","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["15\u2013Deoxy\u2010\u0394\n                    <sup>12<\/sup>\n                    \u2019\n                    <sup>14<\/sup>\n                    \u2010prostaglandin J\n                    <sub>2<\/sub>\n                    inhibits HIV\u20101 transactivating protein, Tat, through covalent modification"],"prefix":"10.1096","volume":"23","author":[{"given":"Parisa","family":"Kalantari","sequence":"first","affiliation":[{"name":"The Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis Department of Veterinary and Biomedical Sciences The Pennsylvania State University University Park Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Narayan","sequence":"additional","affiliation":[{"name":"The Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis Department of Veterinary and Biomedical Sciences The Pennsylvania State University University Park Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Henderson","sequence":"additional","affiliation":[{"name":"Department of Medicine The Center for HIV\/AIDS Care and Research Boston University School of Medicine Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Sandeep","family":"Prabhu","sequence":"additional","affiliation":[{"name":"The Center for Molecular Immunology and Infectious Disease and Center for Molecular Toxicology and Carcinogenesis Department of Veterinary and Biomedical Sciences The Pennsylvania State University University Park Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,3,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.3060"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.665"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0403180"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/330489a0"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb04997.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.9.4045"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90290-0"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-3-48"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603336200"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.13.6377"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.9.3551"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2832944"},{"key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"8366","DOI":"10.1016\/S0021-9258(17)37203-4","article-title":"Intracellular analysis of in vitro modified HIV Tat protein","volume":"269","author":"Koken S. 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