{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:04:40Z","timestamp":1790906680784,"version":"4.1.0"},"reference-count":19,"publisher":"National Academy of Sciences","issue":"36","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,9,5]]},"abstract":"<jats:p>\n                    Microtubules are indispensable dynamic structures that contribute to many essential biological functions. Assembly of the native \u03b1\/\u03b2 tubulin heterodimer, the subunit that polymerizes to form microtubules, requires the participation of several molecular chaperones, namely prefoldin, the cytosolic chaperonin CCT, and a series of five tubulin-specific chaperones termed cofactors A\u2013E (TBCA\u2013E). Among these, TBCC, TBCD, and TBCE are essential in higher eukaryotes; they function together as a multimolecular machine that assembles quasinative CCT-generated \u03b1- and \u03b2-tubulin polypeptides into new heterodimers. Deletion and truncation mutations in the gene encoding TBCE have been shown to cause the rare autosomal recessive syndrome known as HRD, a devastating disorder characterized by congenital hypoparathyroidism, mental retardation, facial dysmorphism, and extreme growth failure. Here we identify cryptic translational initiation at each of three out-of-frame AUG codons upstream of the genetic lesion as a unique mechanism that rescues a mutant HRD allele by producing a functional TBCE protein. Our data explain how afflicted individuals, who would otherwise lack the capacity to make functional TBCE, can survive and point to a limiting capacity to fold tubulin heterodimers\n                    <jats:italic>de novo<\/jats:italic>\n                    as a contributing factor to disease pathogenesis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0602798103","type":"journal-article","created":{"date-parts":[[2006,8,28]],"date-time":"2006-08-28T22:10:40Z","timestamp":1156803040000},"page":"13491-13496","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":31,"title":["Cryptic out-of-frame translational initiation of TBCE rescues tubulin formation in compound heterozygous HRD"],"prefix":"10.1073","volume":"103","author":[{"given":"Guoling","family":"Tian","sequence":"first","affiliation":[{"name":"*Department of Biochemistry, New York University Medical Center, 550 First Avenue, New York, NY 10016;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa C.","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruti","family":"Parvari","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics and Virology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Diaz","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Cowan","sequence":"additional","affiliation":[{"name":"*Department of Biochemistry, New York University Medical Center, 550 First Avenue, New York, NY 10016;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,9,5]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.19.9111"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.19.9116"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.132.1.1"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.41.23910"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80100-2"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.138.4.821"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.149.5.1087"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)01288-5"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3233(01)59003-8"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.10.9.2987"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.112.12.1979"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.221702"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.34.24054"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1515\/JPEM.2004.17.12.1583"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1012"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.107.7.1909"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/86920"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/9.20.5233"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90622-J"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0602798103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T15:12:10Z","timestamp":1649776330000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0602798103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,9,5]]},"references-count":19,"journal-issue":{"issue":"36","published-print":{"date-parts":[[2006,9,5]]}},"alternative-id":["10.1073\/pnas.0602798103"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0602798103","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,9,5]]},"assertion":[{"value":"2006-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-09-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}