ZEB1 explained

Zinc finger E-box-binding homeobox 1 is a protein that in humans is encoded by the ZEB1 gene.^{[1] [2] [3]}

ZEB1 (previously known as TCF8) encodes a zinc finger and homeodomain transcription factor that represses T-lymphocyte-specific IL2 gene expression by binding to a negative regulatory domain 100 nucleotides 5-prime of the IL2 transcription start site.^[2] ZEB1 and its mammalian paralog ZEB2 belongs to the Zeb family within the ZF (zinc finger) class of homeodomain transcription factors. ZEB1 protein has seven zinc fingers and one homeodomain.^[4] The structure of the homeodomain is shown on the right.

Clinical significance

Mutations of the gene are linked to posterior polymorphous corneal dystrophy 3. ZEB1 downregulates E-cadherin and induces epithelial to mesenchymal transition in breast and other carcinomas^[5] A recent study suggested its contributing role in lung cancer invasiveness and metastasis development.^[6] Overexpression of ZEB1 has been identified as a potential risk factor for recurrence and poor prognosis in several types of cancers.^[7]

Further reading

• Franklin AJ, Jetton TL, Shelton KD, Magnuson MA . BZP, a novel serum-responsive zinc finger protein that inhibits gene transcription . Molecular and Cellular Biology . 14 . 10 . 6773–88 . October 1994 . 7935395 . 359208 . 10.1128/MCB.14.10.6773.
• Watanabe Y, Kawakami K, Hirayama Y, Nagano K . Transcription factors positively and negatively regulating the Na,K-ATPase alpha 1 subunit gene . Journal of Biochemistry . 114 . 6 . 849–55 . December 1993 . 8138542 . 10.1093/oxfordjournals.jbchem.a124267.
• Ikeda K, Halle JP, Stelzer G, Meisterernst M, Kawakami K . Involvement of negative cofactor NC2 in active repression by zinc finger-homeodomain transcription factor AREB6 . Molecular and Cellular Biology . 18 . 1 . 10–8 . January 1998 . 9418848 . 121442 . 10.1128/mcb.18.1.10 .
• Turner J, Crossley M . Cloning and characterization of mCtBP2, a co-repressor that associates with basic Krüppel-like factor and other mammalian transcriptional regulators . The EMBO Journal . 17 . 17 . 5129–40 . September 1998 . 9724649 . 1170841 . 10.1093/emboj/17.17.5129 .
• Postigo AA, Dean DC . ZEB represses transcription through interaction with the corepressor CtBP . Proceedings of the National Academy of Sciences of the United States of America . 96 . 12 . 6683–8 . June 1999 . 10359772 . 21975 . 10.1073/pnas.96.12.6683 . 1999PNAS...96.6683P . free .
• Hlubek F, Löhberg C, Meiler J, Jung A, Kirchner T, Brabletz T . Tip60 is a cell-type-specific transcriptional regulator . Journal of Biochemistry . 129 . 4 . 635–41 . April 2001 . 11275565 . 10.1093/oxfordjournals.jbchem.a002901 .
• Locklin RM, Riggs BL, Hicok KC, Horton HF, Byrne MC, Khosla S . Assessment of gene regulation by bone morphogenetic protein 2 in human marrow stromal cells using gene array technology . Journal of Bone and Mineral Research . 16 . 12 . 2192–204 . December 2001 . 11760832 . 10.1359/jbmr.2001.16.12.2192 . 25397480 . free .
• Shaheduzzaman S, Krishnan V, Petrovic A, Bittner M, Meltzer P, Trent J, Venkatesan S, Zeichner S . Effects of HIV-1 Nef on cellular gene expression profiles . Journal of Biomedical Science . 9 . 1 . 82–96 . 2002 . 11810028 . 10.1007/BF02256581 .
• Guaita S, Puig I, Franci C, Garrido M, Dominguez D, Batlle E, Sancho E, Dedhar S, De Herreros AG, Baulida J . Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression . The Journal of Biological Chemistry . 277 . 42 . 39209–16 . October 2002 . 12161443 . 10.1074/jbc.M206400200 . free .
• Costantino ME, Stearman RP, Smith GE, Darling DS . Cell-specific phosphorylation of Zfhep transcription factor . Biochemical and Biophysical Research Communications . 296 . 2 . 368–73 . August 2002 . 12163027 . 10.1016/S0006-291X(02)00880-X . 3682420 .
• Postigo AA . Opposing functions of ZEB proteins in the regulation of the TGFbeta/BMP signaling pathway . The EMBO Journal . 22 . 10 . 2443–52 . May 2003 . 12743038 . 155983 . 10.1093/emboj/cdg225 .
• Postigo AA, Depp JL, Taylor JJ, Kroll KL . Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins . The EMBO Journal . 22 . 10 . 2453–62 . May 2003 . 12743039 . 155984 . 10.1093/emboj/cdg226 .
• Dillner NB, Sanders MM . Transcriptional activation by the zinc-finger homeodomain protein delta EF1 in estrogen signaling cascades . DNA and Cell Biology . 23 . 1 . 25–34 . January 2004 . 14965470 . 10.1089/104454904322745907 .
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proceedings of the National Academy of Sciences of the United States of America . 101 . 33 . 12130–5 . August 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . 2004PNAS..10112130B . free .
• Shimizu S, Krafchak C, Fuse N, Epstein MP, Schteingart MT, Sugar A, Eibschitz-Tsimhoni M, Downs CA, Rozsa F, Trager EH, Reed DM, Boehnke M, Moroi SE, Richards JE . A locus for posterior polymorphous corneal dystrophy (PPCD3) maps to chromosome 10 . American Journal of Medical Genetics. Part A . 130A . 4 . 372–7 . November 2004 . 15384081 . 1249494 . 10.1002/ajmg.a.30267 .

Notes and References

1. Williams TM, Montoya G, Wu Y, Eddy RL, Byers MG, Shows TB . The TCF8 gene encoding a zinc finger protein (Nil-2-a) resides on human chromosome 10p11.2 . Genomics . 14 . 1 . 194–6 . September 1992 . 1427828 . 10.1016/S0888-7543(05)80307-6 .
2. Williams TM, Moolten D, Burlein J, Romano J, Bhaerman R, Godillot A, Mellon M, Rauscher FJ, Kant JA . Identification of a zinc finger protein that inhibits IL-2 gene expression . Science . 254 . 5039 . 1791–4 . December 1991 . 1840704 . 10.1126/science.1840704 . 1991Sci...254.1791W .
3. Web site: Entrez Gene: ZEB1 zinc finger E-box binding homeobox 1.
4. Bürglin TR, Affolter M . Homeodomain proteins: an update . Chromosoma . 125 . 3 . 497–521 . July 2016 . 26464018 . 4901127 . 10.1007/s00412-015-0543-8 .
5. Eger A, Aigner K, Sonderegger S, Dampier B, Oehler S, Schreiber M, Berx G, Cano A, Beug H, Foisner R . DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells . Oncogene . 24 . 14 . 2375–85 . March 2005 . 15674322 . 10.1038/sj.onc.1208429 . free.
6. Liu W, Huang YJ, Liu C, Yang YY, Liu H, Cui JG, Cheng Y, Gao F, Cai JM, Li BL . Inhibition of TBK1 attenuates radiation-induced epithelial-mesenchymal transition of A549 human lung cancer cells via activation of GSK-3β and repression of ZEB1 . Laboratory Investigation; A Journal of Technical Methods and Pathology . 94 . 4 . 362–70 . April 2014 . 24468793 . 10.1038/labinvest.2013.153 . free .
7. Lu J, Fei F, Wu C, Mei J, Xu J, Lu P . ZEB1: Catalyst of immune escape during tumor metastasis . Biomed Pharmacother . 153 . 113490 . September 2022 . 36076506 . 10.1016/j.biopha.2022.113490 . free .