{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:18:41Z","timestamp":1789953521410,"version":"4.0.1"},"reference-count":23,"publisher":"Frontiers Media SA","issue":"11","license":[{"start":{"date-parts":[[2015,2,16]],"date-time":"2015-02-16T00:00:00Z","timestamp":1424044800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Exp Biol Med (Maywood)"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:p>\n                    The regulation of hypoxia-inducible factor-1 (HIF-1) transcriptional activity in the nucleus is related to factor inhibiting HIF-1 (FIH-1). FIH-1 hydrolyzes asparagine at the C-terminal of HIF-1\u03b1, preventing the interaction between HIF-1\u03b1 and its associated cofactors, and leading to suppressed activation of HIF-1. FIH-1 is a cytosolic protein and its entry to the nucleus has to be coordinated with HIF-1\u03b1. The present study was undertaken to examine the correlation between HIF-1\u03b1 and FIH-1 in their nuclear entry. Human umbilical vein endothelial cells were treated with dimethyloxalylglycine at a final concentration of 100\u2009\u00b5M for 4\u2009h, resulting in an accumulation of HIF-1\u03b1 and an increase of FIH-1 in the nucleus as determined by Western blot analysis. Pretreatment of the cells with copper (Cu) chelator tetraethylenepentamine at 50\u2009\u00b5M in cultures for 24\u2009h reduced both HIF-1\u03b1 protein levels and the HIF-1\u03b1 entry to the nucleus, along with decreased FIH-1 protein levels in the nucleus but no changes in the total FIH-1 protein levels in the cells. These effects were prevented by simultaneous addition of 50\u2009\u00b5M CuSO\n                    <jats:sub>4<\/jats:sub>\n                    with tetraethylenepentamine. Gene-silencing of HIF-1\u03b1 significantly inhibited FIH-1 entry to the nucleus, but did not affect the total protein levels of FIH-1 in the cells. This work demonstrates that the nuclear entry of FIH-1 depends on HIF-1\u03b1. Cu deficiency caused a decrease of HIF-1\u03b1, leading to suppression of FIH-1 entry to the nucleus.\n                  <\/jats:p>","DOI":"10.1177\/1535370215570821","type":"journal-article","created":{"date-parts":[[2015,2,16]],"date-time":"2015-02-16T23:30:11Z","timestamp":1424129411000},"page":"1446-1451","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Featured Article: Hypoxia-inducible factor-1\u03b1 dependent nuclear entry of factor inhibiting HIF-1"],"prefix":"10.3389","volume":"240","author":[{"given":"Ke","family":"Liang","sequence":"first","affiliation":[{"name":"Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-qin","family":"Ding","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Lin","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y James","family":"Kang","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2015,2,16]]},"reference":[{"key":"bibr1-1535370215570821","doi-asserted-by":"publisher","DOI":"10.1101\/gad.991402"},{"key":"bibr2-1535370215570821","doi-asserted-by":"publisher","DOI":"10.1126\/science.1059796"},{"key":"bibr3-1535370215570821","first-page":"26351","volume":"277","author":"Hewitson KS","year":"2002","journal-title":"J 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