From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
ZEB1
Available structures
PDB Ortholog search:
PDBe
RCSB List of PDB id codes
2E19
Identifiers
Aliases
ZEB1 , zinc finger E-box binding homeobox 1, AREB6, BZP, DELTAEF1, FECD6, NIL2A, PPCD3, TCF8, ZFHEP, ZFHX1AExternal IDs
OMIM :
189909
MGI :
1344313
HomoloGene :
31779
GeneCards :
ZEB1
Wikidata
Zinc finger E-box-binding homeobox 1 is a
protein that in humans is encoded by the ZEB1
gene .
[5]
[6]
[7]
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 .
[7]
[6] 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.
[8] 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
[9] A recent study suggested its contributing role in
lung cancer invasiveness and metastasis development.
[10] Overexpression of ZEB1 has been identified as a potential risk factor for recurrence and poor prognosis in several types of cancers.
[11]
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000148516 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000024238 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ Williams TM, Montoya G, Wu Y, Eddy RL, Byers MG, Shows TB (September 1992). "The TCF8 gene encoding a zinc finger protein (Nil-2-a) resides on human chromosome 10p11.2". Genomics . 14 (1): 194–6.
doi :
10.1016/S0888-7543(05)80307-6 .
PMID
1427828 .
^
a
b Williams TM, Moolten D, Burlein J, Romano J, Bhaerman R, Godillot A, Mellon M, Rauscher FJ, Kant JA (December 1991). "Identification of a zinc finger protein that inhibits IL-2 gene expression". Science . 254 (5039): 1791–4.
Bibcode :
1991Sci...254.1791W .
doi :
10.1126/science.1840704 .
PMID
1840704 .
^
a
b
"Entrez Gene: ZEB1 zinc finger E-box binding homeobox 1" .
^ Bürglin TR, Affolter M (July 2016).
"Homeodomain proteins: an update" . Chromosoma . 125 (3): 497–521.
doi :
10.1007/s00412-015-0543-8 .
PMC
4901127 .
PMID
26464018 .
^ Eger A, Aigner K, Sonderegger S, Dampier B, Oehler S, Schreiber M, Berx G, Cano A, Beug H, Foisner R (March 2005).
"DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells" . Oncogene . 24 (14): 2375–85.
doi :
10.1038/sj.onc.1208429 .
PMID
15674322 .
^ Liu W, Huang YJ, Liu C, Yang YY, Liu H, Cui JG, Cheng Y, Gao F, Cai JM, Li BL (April 2014).
"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.
doi :
10.1038/labinvest.2013.153 .
PMID
24468793 .
^ Lu J, Fei F, Wu C, Mei J, Xu J, Lu P (September 2022).
"ZEB1: Catalyst of immune escape during tumor metastasis" . Biomed Pharmacother . 153 : 113490.
doi :
10.1016/j.biopha.2022.113490 .
PMID
36076506 .
Further reading
Franklin AJ, Jetton TL, Shelton KD, Magnuson MA (October 1994).
"BZP, a novel serum-responsive zinc finger protein that inhibits gene transcription" . Molecular and Cellular Biology . 14 (10): 6773–88.
doi :
10.1128/MCB.14.10.6773 .
PMC
359208 .
PMID
7935395 .
Watanabe Y, Kawakami K, Hirayama Y, Nagano K (December 1993). "Transcription factors positively and negatively regulating the Na,K-ATPase alpha 1 subunit gene". Journal of Biochemistry . 114 (6): 849–55.
doi :
10.1093/oxfordjournals.jbchem.a124267 .
PMID
8138542 .
Ikeda K, Halle JP, Stelzer G, Meisterernst M, Kawakami K (January 1998).
"Involvement of negative cofactor NC2 in active repression by zinc finger-homeodomain transcription factor AREB6" . Molecular and Cellular Biology . 18 (1): 10–8.
doi :
10.1128/mcb.18.1.10 .
PMC
121442 .
PMID
9418848 .
Turner J, Crossley M (September 1998).
"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.
doi :
10.1093/emboj/17.17.5129 .
PMC
1170841 .
PMID
9724649 .
Postigo AA, Dean DC (June 1999).
"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.
Bibcode :
1999PNAS...96.6683P .
doi :
10.1073/pnas.96.12.6683 .
PMC
21975 .
PMID
10359772 .
Hlubek F, Löhberg C, Meiler J, Jung A, Kirchner T, Brabletz T (April 2001). "Tip60 is a cell-type-specific transcriptional regulator". Journal of Biochemistry . 129 (4): 635–41.
doi :
10.1093/oxfordjournals.jbchem.a002901 .
PMID
11275565 .
Locklin RM, Riggs BL, Hicok KC, Horton HF, Byrne MC, Khosla S (December 2001).
"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.
doi :
10.1359/jbmr.2001.16.12.2192 .
PMID
11760832 .
S2CID
25397480 .
Shaheduzzaman S, Krishnan V, Petrovic A, Bittner M, Meltzer P, Trent J, Venkatesan S, Zeichner S (2002). "Effects of HIV-1 Nef on cellular gene expression profiles". Journal of Biomedical Science . 9 (1): 82–96.
doi :
10.1007/BF02256581 .
PMID
11810028 .
Guaita S, Puig I, Franci C, Garrido M, Dominguez D, Batlle E, Sancho E, Dedhar S, De Herreros AG, Baulida J (October 2002).
"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.
doi :
10.1074/jbc.M206400200 .
PMID
12161443 .
Costantino ME, Stearman RP, Smith GE, Darling DS (August 2002).
"Cell-specific phosphorylation of Zfhep transcription factor" . Biochemical and Biophysical Research Communications . 296 (2): 368–73.
doi :
10.1016/S0006-291X(02)00880-X .
PMC
3682420 .
PMID
12163027 .
Postigo AA (May 2003).
"Opposing functions of ZEB proteins in the regulation of the TGFbeta/BMP signaling pathway" . The EMBO Journal . 22 (10): 2443–52.
doi :
10.1093/emboj/cdg225 .
PMC
155983 .
PMID
12743038 .
Postigo AA, Depp JL, Taylor JJ, Kroll KL (May 2003).
"Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins" . The EMBO Journal . 22 (10): 2453–62.
doi :
10.1093/emboj/cdg226 .
PMC
155984 .
PMID
12743039 .
Dillner NB, Sanders MM (January 2004). "Transcriptional activation by the zinc-finger homeodomain protein delta EF1 in estrogen signaling cascades". DNA and Cell Biology . 23 (1): 25–34.
doi :
10.1089/104454904322745907 .
PMID
14965470 .
Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (August 2004).
"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.
Bibcode :
2004PNAS..10112130B .
doi :
10.1073/pnas.0404720101 .
PMC
514446 .
PMID
15302935 .
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 (November 2004).
"A locus for posterior polymorphous corneal dystrophy (PPCD3) maps to chromosome 10" . American Journal of Medical Genetics. Part A . 130A (4): 372–7.
doi :
10.1002/ajmg.a.30267 .
PMC
1249494 .
PMID
15384081 .
External links
(1) Basic domains
(1.1) Basic
leucine zipper (
bZIP )(1.2) Basic helix-loop-helix (
bHLH )
Group A Group B Group C bHLH-
PAS Group D Group E Group F bHLH-COE
(1.3)
bHLH-ZIP (1.4) NF-1 (1.5) RF-X (1.6) Basic helix-span-helix (bHSH)
(2)
Zinc finger DNA-binding domains
(2.1)
Nuclear receptor (Cys4 )
subfamily 1 subfamily 2 subfamily 3 subfamily 4 subfamily 5 subfamily 6 subfamily 0
(2.2) Other Cys4 (2.3) Cys2 His2 (2.4) Cys6 (2.5) Alternating composition (2.6) WRKY
(4) β-Scaffold factors with minor groove contacts
(0) Other transcription factors