{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T02:20:29Z","timestamp":1773886829596,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T00:00:00Z","timestamp":1561420800000},"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\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM115389"],"award-info":[{"award-number":["R01GM115389"]}],"id":[{"id":"10.13039\/100000057","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":[[2019,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Thyroid transcription factor 1 (TTF1) regulates the tissue\u2010specific expression of genes. However, the molecular regulation of TTF1 in thyroid normal and carcinoma cells has not been revealed. Here we identify 2 distinct ubiquitin E3 ligases that are responsible for TTF1 degradation in normal thyroid cells and carcinoma cells, respectively. Phorbol myristate acetate induced TTF1 protein degradation in the ubiquitin\u2010proteasome system in both HTori3 thyroid follicular epithelial cells and follicular thyroid carcinoma 133 (FTC133) cells. Lysine 151 residue was identified as a ubiquitin acceptor site within TTF1 in both cell types. Overexpression of E3 ubiquitin protein ligase 1 containing HECT, C2, and WW domain (HECW1) induced TTF1 degradation and ubiquitination in Htori3 cells but not in FTC133 cells. Overexpression of ubiquitin E3 ligase subunit FBXL19 increased TTF1 ubiquitination and degradation in FTC133 cells, but it had no effect on TTF1 levels in Htori3 cells. Overexpression of TTF1 increased thyroglobulin and sodium\/iodide symporter mRNA levels, cell migration, and proliferation in HTori3 cells, whereas the effects were reversed by the overexpression of HECW1. This study reveals an undiscovered molecular mechanism by which TTF1 ubiquitination and degradation is regulated by different E3 ligases in thyroid normal and tumor cells.\u2014Liu, J., Dong, S., Wang, H., Li, L., Ye, Q., Li, Y., Miao, J., Jhiang, S., Zhao, J., Zhao, Y. Two distinct E3 ligases, SCF\n                    <jats:sup>FBXL19<\/jats:sup>\n                    and HECW1, degrade thyroid transcription factor 1 in normal thyroid epithelial and follicular thyroid carcinoma cells, respectively. FASEB J. 33, 10538\u201310550 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201900415r","type":"journal-article","created":{"date-parts":[[2019,6,25]],"date-time":"2019-06-25T18:47:55Z","timestamp":1561488475000},"page":"10538-10550","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Two distinct E3 ligases, SCF\n                    <sup>FBXL19<\/sup>\n                    and HECW1, degrade thyroid transcription factor 1 in normal thyroid epithelial and follicular thyroid carcinoma cells, respectively"],"prefix":"10.1096","volume":"33","author":[{"given":"Jia","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Thyroid Surgery The First Hospital of Jilin University  Changchun China"},{"name":"Department of Anesthesia The First Hospital of Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Anesthesia The First Hospital of Jilin University  Changchun China"},{"name":"Department of Physiology and Cell Biology The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesia The First Hospital of Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesia The First Hospital of Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinmao","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Anesthesia The First Hospital of Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesia The First Hospital of Jilin University  Changchun China"},{"name":"Department of Physiology and Cell Biology The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaxing","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Anesthesia The First Hospital of Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sissy","family":"Jhiang","sequence":"additional","affiliation":[{"name":"Department of Anesthesia The First Hospital of Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Anesthesia The First Hospital of Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Anesthesia The First Hospital of Jilin University  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,6,25]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"3640","article-title":"Transcriptional activation of the thyroglobulin promoter directing suicide gene expression by thyroid transcription factor\u20101 in thyroid cancer cells","volume":"61","author":"Shimura H.","year":"2001","journal-title":"Cancer Res."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20080068"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0214192"},{"key":"e_1_2_8_5_1","first-page":"654","article-title":"The molecular causes of thyroid dysgenesis: a systematic review","volume":"36","author":"Nettore I. 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