{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T10:38:31Z","timestamp":1775558311458,"version":"3.50.1"},"reference-count":21,"publisher":"Proceedings of the National Academy of Sciences","issue":"17","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,8,14]]},"abstract":"<jats:p>\n            Hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1)\n            <jats:sup>1<\/jats:sup>\n            is a global\n transcriptional regulator of the hypoxic response. Under normoxic\n conditions, HIF-1\u03b1 is recognized by the von Hippel-Lindau\n tumor-suppressor protein (VHL), a component of an E3 ubiquitin ligase\n complex. This interaction thereby promotes the rapid degradation of\n HIF-1\u03b1. Under hypoxic conditions, HIF-1\u03b1 is stabilized. We have\n previously shown that VHL binds in a hypoxia-sensitive manner to a\n 27-aa segment of HIF-1\u03b1, and that this regulation depends on a\n posttranslational modification of HIF-1\u03b1. Through a combination of\n            <jats:italic>in vivo<\/jats:italic>\n            coimmunoprecipitation assays using VHL and a\n panel of point mutants of HIF-1\u03b1 in this region, as well as MS and\n            <jats:italic>in vitro<\/jats:italic>\n            binding assays, we now provide evidence that\n this modification, which occurs under normoxic conditions, is\n hydroxylation of Pro-564 of HIF-1\u03b1. The data furthermore show that\n this proline hydroxylation is the primary regulator of VHL binding.\n          <\/jats:p>","DOI":"10.1073\/pnas.181341498","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:37:36Z","timestamp":1027694256000},"page":"9630-9635","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":692,"title":["HIF-1\u03b1 binding to VHL is regulated by stimulus-sensitive proline hydroxylation"],"prefix":"10.1073","volume":"98","author":[{"given":"Fang","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of\r Pennsylvania Cancer Center, University of Pennsylvania School of\r Medicine, 605 Stellar-Chance Laboratories, 422 Curie Boulevard,\r Philadelphia, PA 19104"}]},{"given":"Sarah B.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of\r Pennsylvania Cancer Center, University of Pennsylvania School of\r Medicine, 605 Stellar-Chance Laboratories, 422 Curie Boulevard,\r Philadelphia, PA 19104"}]},{"given":"Quan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of\r Pennsylvania Cancer Center, University of Pennsylvania School of\r Medicine, 605 Stellar-Chance Laboratories, 422 Curie Boulevard,\r Philadelphia, PA 19104"}]},{"given":"Frank S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of\r Pennsylvania Cancer Center, University of Pennsylvania School of\r Medicine, 605 Stellar-Chance Laboratories, 422 Curie Boulevard,\r Philadelphia, PA 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