ZEB1 , "ZFHEP (10p11.22), "Zn Finger E-box Homeobox1"

 https://www.ncbi.nlm.nih.gov/gene/6935
Tällä sinkkisormi-transkriptiofaktorilla on tehtävää interleukiini2:n vaimentajana. Mutaatiot assosioituvat silmäsairauksiin. Niistä geeni saakin useita nimilyhennyksiä. Rakennenimi ZFHEP kertoo että se on sinkkisormiproteiini jolla on E-box ja Homeo-box.

Also known as BZP; TCF8; AREB6; FECD6; NIL2A; PPCD3; ZFHEP; ZFHX1A; DELTAEF1

Summary This gene encodes a zinc finger transcription factor. The encoded protein likely plays a role in transcriptional repression of interleukin 2. Mutations in this gene have been associated with posterior polymorphous corneal dystrophy-3 and late-onset Fuchs endothelial corneal dystrophy. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Mar 2010]

Expression Ubiquitous expression in endometrium (RPKM 12.8), brain (RPKM 12.1) and 23 other tissues See more Orthologs mouse all

 

Preferred Names

zinc finger E-box-binding homeobox 1

Names

delta-crystallin enhancer binding factor 1;  (DELTAEF1)

negative regulator of IL2;  (NIL2A)

posterior polymorphous corneal dystrophy 3;(PPCD3)

transcription factor 8 (represses interleukin 2 expression); (TCF8)

zinc finger homeodomain enhancer-binding protein; (ZFHEP)

NP_001121600.1  zinc finger E-box-binding homeobox 1 isoform a

See identical proteins and their annotated locations for NP_001121600.1

Description

Transcript Variant: This variant (1) encodes isoform a.

Conserved Domains (5) summary

smart00389
Location:577 → 613

HOX; Homeodomain

COG5048
Location:913 → 966

COG5048; FOG: Zn-finger [General function prediction only]

sd00017
Location:890 → 910

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00096
Location:224 → 246

zf-C2H2; Zinc finger, C2H2 type

pfam13465
Location:930 → 955

zf-H2C2_2; Zinc-finger double domain

Related articles in PubMed

1. ZEB1 mediates doxorubicin (Dox) resistance and mesenchymal characteristics of hepatocarcinoma cells. Long L, et al. Exp Mol Pathol, 2019 Feb. PMID 30615851
2. Zinc finger E-box-binding homeobox 1 (ZEB1) is required for neural differentiation of human embryonic stem cells. Jiang Y, et al. J Biol Chem, 2018 Dec 14. PMID 30337365,
3. Radiation exposure triggers the progression of triple negative breast cancer via stabilizing ZEB1. Lin Y, et al. Biomed Pharmacother, 2018 Nov. PMID 30257380
4. Zeb1 potentiates genome-wide gene transcription with Lef1 to promote glioblastoma cell invasion. Rosmaninho P, et al. EMBO J, 2018 Aug 1. PMID 29903919,
5. Knockdown of ZEB1 suppressed the formation of vasculogenic mimicry and epithelial-mesenchymal transition in the human breast cancer cell line MDA-MB-231. Liang W, et al. Mol Med Rep, 2018 May. PMID 29512767
   Mol Med Rep. 2018 May;17(5):6711-6716. doi: 10.3892/mmr.2018.8677. Epub 2018 Mar 5.
   Breast cancer is a common malignant tumor in women. It has been suggested that a type of microcirculation pattern that does not rely on host microvascular endothelial cells known as vasculogenic mimicry (VM) may contribute to the poor effect of anti‑angiogenesis treatment on some patients with breast cancer. However, the formation and regulatory mechanism of VM in breast cancer are unclear and still require further investigation. The present study examined whether decreasing the expression of zinc finger E‑box binding homeobox (ZEB1) using siRNA can inhibit the formation of VM in Triple Negative Breast Cancer (TNBC), and its specific function and molecular mechanism. mRNA and protein expression were detected by RT‑qPCR and western blotting. Invasion assay and tube formation assay were also performed. The results demonstrated that ZEB1 small hairpin (sh)RNA inhibited the formation of VM. Knockdown of ZEB1 markedly inhibited the expression of vimentin in MDA‑MB‑231 cells and markedly increased the expression of E‑cadherin. It was suggested that ZEB1 shRNA may have inhibited the epithelial‑mesenchymal transition (EMT). In addition, ZEB1 shRNA inhibited the invasion of MDA‑MB‑231 cells and suppressed the expression of fetal liver kinase 1 (flk‑1). The flk‑1 inhibitor Semaxanib inhibited the formation of VM; thus, ZEB1 shRNA inhibited EMT and cell invasion, and may have inhibited the formation of VM through flk‑1. The present study contributed further understanding on the theory of tumor angiogenesis and provided theoretical basis for novel targeted therapy of TNBC.

See all (402) citations in PubMed

Sirtuiinitekstin yhteydessä oli sivuhuomautuksena asiaa ZEB1-proteiinista jonka SIRT1 rekrytoi.

KUVA2

Kuva 2 esittää kaavamaisesti Sirtuiinien suorittaman positiivisen ja negatiivisen EMT-säätelyn.

Positiivista( = EMT:tä edistävää): TGF-beeta signalointiin liittyy Sirtuiini1- proteiinin lisääntyminen. SIRT1 rekrytoi ZEB1-proteiinin

( ZEB1 on C2H2- sinkkisormiproteiini ja transkriptiofaktori ja osallistuu tuumorin invaasioon ja metaboliaan. Se on EMT:n mestarisäätelijä. Sitä itseään säätelee usea signaalijärjestelmä kuten Wnt, TGF-beeta, NFkB, HIF ja miRNA. Sen onkogeeninen rooli on E-cadheriini- proteiinin tukahduttaminen, onhan E-Cad  tärkein solu-solu-adheesiomolekyyli. ZEB1 pääsee vaikuttamaan E-Cadheriiniin tekemällä interaktion useiden kromatiinia muokkaavan tekijän kanssa, kuten CtBP ja Swi/SNF-kompleksi. Toisaalta ZEB1 aktivoi suoraan niiden geenien promoottoreita, jotka osallistuvat EMT-ohjelmaan. ZEB1 tekee interaktion joko SMAD- proteiinien tai p300/CAF kanssa ja aktivoi TGFbeetan kohdegeenin CDH2 (N-Cadheriinin, joka on mesenkymaalinen cadheriini ja olennainen tuumorin progressiolle). ZEB1- yli-ilmenemä useissa syöpälinjoissa ( havaittu haima-, keuhko-, maksasyövässä, osteosarkoomassa, rintasyövässä, paksusuolisyövässä) indusoi EMT:tä ja edistää solujen invaasiota. Tieto vuodelta 2017) .

• Schematic representation of positive and negative regulation of EMT by sirtuins. Positive: TGF‐β signaling is associated with an increase in Sirt1. Sirt1 is recruited by Zeb1 to the E‐cadherin promoter and causes transcriptional repression.