Skip to main content

Zinc Finger E-Box-Binding Homeobox 2

  • Reference work entry
  • First Online:
  • 21 Accesses

Synonyms

Danio rerio: Zeb2b, sip1b, zfhx1b; Homo sapiens: SIP1, SIP-1, SMADIP1, ZFHX1B; Mus musculus: Zeb2, Zfx1b, Zfhx1b; Xenopus tropicalis: XSip1

Historical Background

Zinc finger E-box-binding homeobox 2 (ZEB2) is a zinc finger and homeodomain transcription factor. ZEB2 was identified as a protein binding to the MH2 domain of different Smad proteins involved in BMP- and TGF-ß pathways (Verschueren et al. 1999). Initial studies correlating ZEB2 and E-cadherin downregulation in carcinomas were followed by a significant amount of research linking ZEB2 and epithelial-to-mesenchymal transition (EMT) during tumor progression (Comijn et al. 2001). Together with its paralog ZEB1, ZEB2 belongs to the Zeb family of transcription factors characterized by two zinc finger clusters separated by a homeodomain. During evolution, the duplication of the ancestral ZEB gene and diversification of ZEB2 from ZEB1 coincide with the onset of neural crest development and specification.

Physiological...

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   4,499.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   4,499.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Abba ML, Patil N, Leupold JH, Allgayer H. MicroRNA regulation of epithelial to mesenchymal transition. J Clin Med. 2016;5(1):8.

    Article  PubMed Central  CAS  Google Scholar 

  • Bindels S, Mestdagt M, Vandewalle C, Jacobs N, Volders L, Noel A, et al. Regulation of vimentin by SIP1 in human epithelial breast tumor cells. Oncogene. 2006;25(36):4975–85.

    Article  CAS  PubMed  Google Scholar 

  • Brabletz S, Brabletz T. The ZEB/miR-200 feedback loop – a motor of cellular plasticity in development and cancer? EMBO Reports. 2010;11(9):670–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Comijn J, Berx G, Vermassen P, Verschueren K, van Grunsven L, Bruyneel E, et al. The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell. 2001;7(6):1267–78.

    Article  CAS  PubMed  Google Scholar 

  • Conidi A, Cazzola S, Beets K, Coddens K, Collart C, Cornelis F, et al. Few Smad proteins and many Smad-interacting proteins yield multiple functions and action modes in TGFbeta/BMP signaling in vivo. Cytokine Growth Factor Rev. 2011;22(5–6):287–300.

    Article  CAS  PubMed  Google Scholar 

  • Dominguez CX, Amezquita RA, Guan T, Marshall HD, Joshi NS, Kleinstein SH, et al. The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection. J Exp Med. 2015;212(12):2041–56.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Espinosa-Parrilla Y, Amiel J, Auge J, Encha-Razavi F, Munnich A, Lyonnet S, et al. Expression of the SMADIP1 gene during early human development. Mech Develop. 2002;114(1–2):187–91.

    Article  CAS  Google Scholar 

  • Gheldof A, Hulpiau P, van Roy F, De Craene B, Berx G. Evolutionary functional analysis and molecular regulation of the ZEB transcription factors. Cell Mol Life Sci. 2012;69(15):2527–41.

    Article  CAS  PubMed  Google Scholar 

  • Goossens S, Janzen V, Bartunkova S, Yokomizo T, Drogat B, Crisan M, et al. The EMT regulator Zeb2/Sip1 is essential for murine embryonic hematopoietic stem/progenitor cell differentiation and mobilization. Blood. 2011;117(21):5620–30.

    Article  CAS  PubMed  Google Scholar 

  • Grande MT, Sanchez-Laorden B, Lopez-Blau C, De Frutos CA, Boutet A, Arevalo M, et al. Snail1-induced partial epithelial-to-mesenchymal transition drives renal fibrosis in mice and can be targeted to reverse established disease. Nat Med. 2015;21(9):989–97.

    Article  CAS  PubMed  Google Scholar 

  • Gregory PA, Bracken CP, Smith E, Bert AG, Wright JA, Roslan S, et al. An autocrine TGF-beta/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition. Mol Biol Cell. 2011;22(10):1686–98.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hegarty SV, Sullivan AM, O’Keeffe GW. Zeb2: a multifunctional regulator of nervous system development. Prog Neurobiol. 2015;132:81–95.

    Article  CAS  PubMed  Google Scholar 

  • Hill L, Browne G, Tulchinsky E. ZEB/miR-200 feedback loop: at the crossroads of signal transduction in cancer. Int J Cancer. 2013;132(4):745–54.

    Article  CAS  PubMed  Google Scholar 

  • Iwano M, Plieth D, Danoff TM, Xue C, Okada H, Neilson EG. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest. 2002;110(3):341–50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jahan F, Rattan S, Dixon I, Wigle J. Zeb2: a novel regulator of cardiac fibroblast to myofibroblast transition. Faseb J. 2015;29:556.1.

    Google Scholar 

  • Jimenez PT, Mainigi MA, Word RA, Kraus WL, Mendelson CR. miR-200 regulates endometrial development during early pregnancy. Mol Endocrinol. 2016;30(9):977–87.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Katoh M, Katoh M. Integrative genomic analyses of ZEB2: transcriptional regulation of ZEB2 based on SMADs, ETS1, HIF1alpha, POU/OCT, and NF-kappaB. Int J Oncol. 2009;34(6):1737–42.

    Article  CAS  PubMed  Google Scholar 

  • Koopmansch B, Berx G, Foidart JM, Gilles C, Winkler R. Interplay between KLF4 and ZEB2/SIP1 in the regulation of E-cadherin expression. Biochem Biophys Res Commun. 2013;431(4):652–7.

    Article  CAS  PubMed  Google Scholar 

  • Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133(4):704–15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mowat DR, Wilson MJ, Goossens M. Mowat-Wilson syndrome. J Med Genet. 2003;40(5):305–10.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Oba S, Kumano S, Suzuki E, Nishimatsu H, Takahashi M, Takamori H, et al. miR-200b precursor can ameliorate renal tubulointerstitial fibrosis. PloS One. 2010;5(10):e13614.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Omilusik KD, Best JA, Yu B, Goossens S, Weidemann A, Nguyen JV, et al. Transcriptional repressor ZEB2 promotes terminal differentiation of CD8+ effector and memory T cell populations during infection. J Exp Med. 2015;212(12):2027–39.

    Article  PubMed  PubMed Central  Google Scholar 

  • Puisieux A, Brabletz T, Caramel J. Oncogenic roles of EMT-inducing transcription factors. Nat Cell Biol. 2014;16(6):488–94.

    Article  CAS  PubMed  Google Scholar 

  • Sanchez-Tillo E, Siles L, de Barrios O, Cuatrecasas M, Vaquero EC, Castells A, et al. Expanding roles of ZEB factors in tumorigenesis and tumor progression. Am J Cancer Res. 2011;1(7):897–912.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Scott CL, Soen B, Martens L, Skrypek N, Saelens W, Taminau J, et al. The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2. J Exp Med. 2016;213(6):897–911.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871–90.

    Article  CAS  PubMed  Google Scholar 

  • Verschueren K, Remacle JE, Collart C, Kraft H, Baker BS, Tylzanowski P, et al. SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5′-CACCT sequences in candidate target genes. J Biol Chem. 1999;274(29):20489–98.

    Article  CAS  PubMed  Google Scholar 

  • Van de Putte T, Francis A, Nelles L, van Grunsven LA, Huylebroeck D. Neural crest-specific removal of Zfhx1b in mouse leads to a wide range of neurocristopathies reminiscent of Mowat-Wilson syndrome. Hum Mol Genet. 2007;16(12):1423–36.

    Article  CAS  PubMed  Google Scholar 

  • van Helden MJ, Goossens S, Daussy C, Mathieu AL, Faure F, Marcais A, et al. Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection. J Exp Med. 2015;212(12):2015–25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vandamme N, Berx G. Melanoma cells revive an embryonic transcriptional network to dictate phenotypic heterogeneity. Front Oncol. 2014;4:352.

    Article  PubMed  PubMed Central  Google Scholar 

  • Vandewalle C, Van Roy F, Berx G. The role of the ZEB family of transcription factors in development and disease. Cell Mol Life Sci. 2009;66(5):773–87.

    Article  CAS  PubMed  Google Scholar 

  • Wong TS, Gao W, Chan JY. Transcription regulation of E-cadherin by zinc finger E-box binding homeobox proteins in solid tumors. Biomed Res Int. 2014;2014:921564.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Geert Berx .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Akay, Ö., Bruneel, K., Soen, B., De Smedt, E., Vandamme, N., Berx, G. (2018). Zinc Finger E-Box-Binding Homeobox 2. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101944

Download citation

Publish with us

Policies and ethics