Transcriptional Regulation by VENTX

Stable Identifier
R-HSA-8853884
Type
Pathway
Species
Homo sapiens
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this pathway in the Pathway Browser

The VENTX (also known as VENT homeobox or VENTX2) gene is a member of the homeobox family of transcription factors. The ortholog of VENTX was first described in Xenopus where it participates in BMP and Nanog signaling pathways and controls dorsoventral mesoderm patterning (Onichtchouk et al. 1996, Scerbo et al. 2012). The zebrafish ortholog of VENTX is also involved in dorsoventral patterning in the early embryo (Imai et al. 2001). Rodents lack the VENTX ortholog (Zhong and Holland 2011). VENTX is expressed in human blood cells (Moretti et al. 2001) and appears to play an important role in hematopoiesis. The role of VENTX in hematopoiesis was first suggested based on its role in mesoderm patterning in Xenopus and zebrafish (Davidson and Zon 2000). VENTX promotes cell cycle arrest and differentiation of hematopoietic stem cells and/or progenitor cells (Wu, Gao, Ke, Giese and Zhu 2011, Wu et al. 2014). Ventx suppression leads to expansion of hematopoietic stem cells and multi-progenitor cells (Gao et, J. Biol.Chem, 2012). VENTX induces transcription of cell cycle inhibitors TP53 (p53) and p16INK4A and activates tumor suppressor pathways regulated by TP53 and p16INK4A (Wu, Gao, Ke, Hager et al. 2011), as well as macrophage colony stimulating factor receptor (CSF1R) (Wu, Gao, Ke, Giese and Zhu 2011) and inhibits transcription of cyclin D1 (CCND1) (Gao et al. 2010) and Interleukin-6 (IL6) (Wu et al. 2014). Chromatin immunoprecipitation showed that EGR3 transcription factor directly binds to the promoter of IL6 and IL8 genes (Baron VT et al, BJC 2015). While VENTX expression may suppress lymphocytic leukemia (Gao et al. 2010), high levels of VENTX have been reported in acute myeloid leukemia cells, with a positive effect on their proliferation (Rawat et al. 2010). Another homeobox transcription factor that regulates differentiation of hematopoietic stemm cells is DLX4 (Bon et al. 2015). Studies on colon cancer showed that VentX regulates tumor associated macrophages and reverts immune suppression in tumor microenvironment (Le et al. 2018). MEK1 is required for Xenopus Ventx2 asymmetric distribution during blastula cell division. Ventx2 inhibition by MEK1 is required for embryonic cell commitment (Scerbo et al, eLife, 2017). VENTX induces TP53-independent apoptosis in cancer cells (Gao H, Oncotarget, 2016). During Xenopus embryonic development, VENTX ortholog regulates transcription of the sox3 gene (Rogers et al. 2007) as well as the early neuronal gene zic3 (Umair et al. 2018).

Literature References
PubMed ID Title Journal Year
22606298 Ventx factors function as Nanog-like guardians of developmental potential in Xenopus

Scerbo, P, Girardot, F, Vivien, C, Markov, GV, Luxardi, G, Demeneix, B, Kodjabachian, L, Coen, L

PLoS ONE 2012
20028861 VentX, a novel lymphoid-enhancing factor/T-cell factor-associated transcription repressor, is a putative tumor suppressor

Gao, H, Le, Y, Wu, X, Silberstein, LE, Giese, RW, Zhu, Z

Cancer Res. 2010
24706756 Homeobox transcription factor VentX regulates differentiation and maturation of human dendritic cells

Wu, X, Gao, H, Bleday, R, Zhu, Z

J. Biol. Chem. 2014
25633035 Early Growth Response 3 regulates genes of inflammation and directly activates IL6 and IL8 expression in prostate cancer

Baron, VT, Pio, R, Jia, Z, Mercola, D

Br. J. Cancer 2015
27175592 Homeobox protein VentX induces p53-independent apoptosis in cancer cells

Gao, H, Wu, B, Le, Y, Zhu, Z

Oncotarget 2016
26208636 The homeobox gene DLX4 regulates erythro-megakaryocytic differentiation by stimulating IL-1β and NF-κB signaling

Trinh, BQ, Barengo, N, Kim, SB, Lee, JS, Zweidler-McKay, PA, Naora, H

J. Cell. Sci. 2015
21670496 The homeobox transcription factor VentX controls human macrophage terminal differentiation and proinflammatory activation

Wu, X, Gao, H, Ke, W, Giese, RW, Zhu, Z

J. Clin. Invest. 2011
21679462 The dynamics of vertebrate homeobox gene evolution: gain and loss of genes in mouse and human lineages

Zhong, YF, Holland, PW

BMC Evol. Biol. 2011
20833819 The vent-like homeobox gene VENTX promotes human myeloid differentiation and is highly expressed in acute myeloid leukemia

Rawat, VP, Arseni, N, Ahmed, F, Mulaw, MA, Thoene, S, Heilmeier, B, Sadlon, T, D'Andrea, RJ, Hiddemann, W, Bohlander, SK, Buske, C, Feuring-Buske, M

Proc. Natl. Acad. Sci. U.S.A. 2010
29872044 The homeobox protein VentX reverts immune suppression in the tumor microenvironment

Le, Y, Gao, H, Bleday, R, Zhu, Z

Nat Commun 2018
10948449 Turning mesoderm into blood: the formation of hematopoietic stem cells during embryogenesis

Davidson, AJ, Zon, LI

Curr. Top. Dev. Biol. 2000
11493559 The homeobox genes vox and vent are redundant repressors of dorsal fates in zebrafish

Imai, Y, Gates, MA, Melby, AE, Kimelman, D, Schier, AF, Talbot, WS

Development 2001
8898218 The Xvent-2 homeobox gene is part of the BMP-4 signalling pathway controlling [correction of controling] dorsoventral patterning of Xenopus mesoderm

Onichtchouk, D, Gawantka, V, Dosch, R, Delius, H, Hirschfeld, K, Blumenstock, C, Niehrs, C

Development 1996
11549314 Molecular cloning of a human Vent-like homeobox gene

Moretti, PA, Davidson, AJ, Baker, E, Lilley, B, Zon, LI, D'Andrea, RJ

Genomics 2001
18031719 Sox3 expression is maintained by FGF signaling and restricted to the neural plate by Vent proteins in the Xenopus embryo

Rogers, CD, Archer, TC, Cunningham, DD, Grammer, TC, Casey, EM

Dev. Biol. 2008
21325273 VentX trans-activates p53 and p16ink4a to regulate cellular senescence

Wu, X, Gao, H, Ke, W, Hager, M, Xiao, S, Freeman, MR, Zhu, Z

J. Biol. Chem. 2011
30590909 Ventx1.1 as a Direct Repressor of Early Neural Gene zic3 in Xenopus laevis

Umair, Z, Kumar, S, Kim, DH, Rafiq, K, Kumar, V, Kim, S, Park, JB, Lee, JY, Lee, U, Kim, J

Mol. Cells 2018
28654420 Lineage commitment of embryonic cells involves MEK1-dependent clearance of pluripotency regulator Ventx2

Scerbo, P, Marchal, L, Kodjabachian, L

Elife 2017
Participants
Participant Of
Orthologous Events
Authored
Reviewed
Created