{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:18:28Z","timestamp":1792592308774,"version":"4.5.0"},"reference-count":31,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5775","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2006,5,12]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>DKC1<\/jats:italic>\n                    gene encodes a pseudouridine synthase that modifies ribosomal RNA (rRNA).\n                    <jats:italic>DKC1<\/jats:italic>\n                    is mutated in people with X-linked dyskeratosis congenita (X-DC), a disease characterized by bone marrow failure, skin abnormalities, and increased susceptibility to cancer. How alterations in ribosome modification might lead to cancer and other features of the disease remains unknown. Using an unbiased proteomics strategy, we discovered a specific defect in IRES (internal ribosome entry site)\u2013dependent translation in\n                    <jats:italic>\n                      Dkc1\n                      <jats:sup>m<\/jats:sup>\n                    <\/jats:italic>\n                    mice and in cells from X-DC patients. This defect results in impaired translation of messenger RNAs containing IRES elements, including those encoding the tumor suppressor p27(Kip1) and the antiapoptotic factors Bcl-xL and XIAP (X-linked Inhibitor of Apoptosis Protein). Moreover,\n                    <jats:italic>\n                      Dkc1\n                      <jats:sup>m<\/jats:sup>\n                    <\/jats:italic>\n                    ribosomes were unable to direct translation from IRES elements present in viral messenger RNAs. These findings reveal a potential mechanism by which defective ribosome activity leads to disease and cancer.\n                  <\/jats:p>","DOI":"10.1126\/science.1123835","type":"journal-article","created":{"date-parts":[[2006,5,11]],"date-time":"2006-05-11T21:36:40Z","timestamp":1147383400000},"page":"902-906","source":"Crossref","is-referenced-by-count":398,"title":["Impaired Control of IRES-Mediated Translation in X-Linked Dyskeratosis Congenita"],"prefix":"10.1126","volume":"312","author":[{"given":"Andrew","family":"Yoon","sequence":"first","affiliation":[{"name":"Human Genetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA."},{"name":"Center for Cell Based Therapy, Fundac\u0327a\u0303o Hemocentro de Ribeira\u0303o Preto, University of Sao Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Peng","sequence":"additional","affiliation":[{"name":"Human Genetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA."},{"name":"Center for Cell Based Therapy, Fundac\u0327a\u0303o Hemocentro de Ribeira\u0303o Preto, University of Sao Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Brandenburg","sequence":"additional","affiliation":[{"name":"Human Genetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA."},{"name":"Center for Cell Based Therapy, Fundac\u0327a\u0303o Hemocentro de Ribeira\u0303o Preto, University of Sao Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornella","family":"Zollo","sequence":"additional","affiliation":[{"name":"Human Genetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA."},{"name":"Center for Cell Based Therapy, Fundac\u0327a\u0303o Hemocentro de Ribeira\u0303o Preto, University of Sao Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"Human Genetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA."},{"name":"Center for Cell Based Therapy, Fundac\u0327a\u0303o Hemocentro de Ribeira\u0303o Preto, University of Sao Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Rego","sequence":"additional","affiliation":[{"name":"Human Genetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA."},{"name":"Center for Cell Based Therapy, Fundac\u0327a\u0303o Hemocentro de Ribeira\u0303o Preto, University of Sao Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Ruggero","sequence":"additional","affiliation":[{"name":"Human Genetics Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA."},{"name":"Center for Cell Based Therapy, Fundac\u0327a\u0303o Hemocentro de Ribeira\u0303o Preto, University of Sao Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2000.02109.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00412-005-0333-9"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80238-X"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.24.8457-8466.2002"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0402560101"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079447"},{"key":"e_1_3_2_8_2","unstructured":"Materials and methods are available as supporting material on Science 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are indebted to M. Barna for helpful discussions and critical reading of the manuscript. We thank A. Koff for the p27 \u2013\/\u2013 mice; M. Holcik L. Hengst and P. Sarnow for reagents; K. Zaret J. Burch E. Golemis and J. Testa for critical reading of the manuscript; and FCCC core facilities and J. Grant for technical assistance."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1123835","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T22:39:58Z","timestamp":1704839998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1123835"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,5,12]]},"references-count":31,"journal-issue":{"issue":"5775","published-print":{"date-parts":[[2006,5,12]]}},"alternative-id":["10.1126\/science.1123835"],"URL":"https:\/\/doi.org\/10.1126\/science.1123835","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.13819.471320","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.13819.793533624","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,5,12]]}}}