XB-ART-58944
Int J Mol Sci
2022 Mar 01;235:. doi: 10.3390/ijms23052741.
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Ventx Family and Its Functional Similarities with Nanog: Involvement in Embryonic Development and Cancer Progression.
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The Ventx family is one of the subfamilies of the ANTP (antennapedia) superfamily and belongs to the NK-like (NKL) subclass. Ventx is a homeobox transcription factor and has a DNA-interacting domain that is evolutionarily conserved throughout vertebrates. It has been extensively studied in Xenopus, zebrafish, and humans. The Ventx family contains transcriptional repressors widely involved in embryonic development and tumorigenesis in vertebrates. Several studies have documented that the Ventx family inhibited dorsal mesodermal formation, neural induction, and head formation in Xenopus and zebrafish. Moreover, Ventx2.2 showed functional similarities to Nanog and Barx1, leading to pluripotency and neural-crest migration in vertebrates. Among them, Ventx protein is an orthologue of the Ventx family in humans. Studies have demonstrated that human Ventx was strongly associated with myeloid-cell differentiation and acute myeloid leukemia. The therapeutic potential of Ventx family inhibition in combating cancer progression in humans is discussed. Additionally, we briefly discuss genome evolution, gene duplication, pseudo-allotetraploidy, and the homeobox family in Xenopus.
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BB/T003146/1 Biotechnology and Biological Sciences Research Council , 2016R1D1A1B02008770 and 2021M3H9A1097557 National Research Foundation of Korea
Species referenced: Xenopus laevis
Genes referenced: barx1 bmp4 chrd gsc ncoa6 ventx1 ventx2.2
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Figure 1. Chromosomal localization of Ventx gene synteny in humans and other animal species relative to adjacent genes (color-coded). |
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Figure 2. Schematic representation of conserved domains and motifs associated with different classes of HD proteins in animals. This figure was adapted from Burglin et al. (2016) [9]. |
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Figure 3. Schematic representations of Ventx domains in Xenopus laevis, zebrafish, and humans. (A) All Ventx members contain a transactivation domain (green), a highly conserved homeobox DNA-binding domain (HD, 60 aa, pink), and a repressor domain (grey), which inhibits the expression of dorsal-specific genes such as gsc, chordin, and boz/dha. The N-terminal domain (ND) of the Ventx family acts as a transactivation domain (TAD) to activate ventral-specific genes such as bmp4, ventx1.1, ventx1.2, Ventx2.2, and Ventx2.2. (B) An evolutionary phylogenetic tree of the Ventx gene cluster in Xenopus laevis. (C) An evolutionary phylogenetic tree of the vega/ventx gene cluster in zebrafish. (B’,C’) The percentage-identity matrix of Ventx family members in Xenopus and zebrafish. |
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Figure 4. Upstream and downstream regulatory pathways for Ventx members during Xenopus laevis and zebrafish embryonic development and the potential functions of Ventx in human hematopoiesis, cell differentiation, and leukemogenesis. Lines with arrows indicate promoting and those with bars suppressing (functions of) the targets. Indirect targets of Ventx family members are in red. Sign (?) indicates unknown factors. |
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