LEF1/TCFs are high mobility group box-containing transcriptional factors mediating canonical Wnt/β-catenin signaling during early embryogenesis and tumorigenesis. β-Catenin forms a complex with LEF 1/TCFs and transa...LEF1/TCFs are high mobility group box-containing transcriptional factors mediating canonical Wnt/β-catenin signaling during early embryogenesis and tumorigenesis. β-Catenin forms a complex with LEF 1/TCFs and transactivates LEF1/TCF-mediated transcriptions during dorsalization. Although LEF-mediated transcription is also implicated in ventralization, the underlying molecular mechanism is not well understood. Using the vertebrate Xenopus laevis model system, we found that Xom, which is a ventralizing homeobox protein with dual roles of transcriptional activation and repression, forms a complex with LEF 1/TCF through its homeodomain and transactivates LEF 1/TCF-mediated transcription through its N-terminal transactivation domain （TAD）. Our data show that Xom lacking the N-terminal TAD fails to transactivate ventral genes, such as BMP4 and Xom itself, but retains the ability to suppress transcriptional activation of dorsal gene promoters, such as the Goosecoid promoter, indicating that transactivation and repression are separable functions of Xom. It has been postulated that Xom forms a positive re-enforcement loop with BMP4 to promote ventral- ization and to suppress dorsal gene expression. Consistent with an essential role of Xom transactivation of LEF1/TCFs during early embryogenesis, we found that expression of the dominant-negative Xom mutant that lacks the TAD fails to re-enforce the ventral signaling of BMP4 and causes a catastrophic effect during gastrulation. Our data suggest that the functional interaction of Xom and LEF 1/TCF-factors is essential for ventral cell fate determination and that LEF 1/TCF factors may function as a point of convergence to mediate the combined signaling of Wnt/β-catenin and BMP4/Xom pathways during early embryogenesis.展开更多
Both the Wnt/β-catenin and Bone morphogenetic protein （Bmp） signaling pathways play critical roles in dorsal-ventral patterning of the Xenopus embryos. The lymphoid enhancer binding factor （Lef） / T cell factor ...Both the Wnt/β-catenin and Bone morphogenetic protein （Bmp） signaling pathways play critical roles in dorsal-ventral patterning of the Xenopus embryos. The lymphoid enhancer binding factor （Lef） / T cell factor （Tcf） have been viewed as dedicated transcription factors of the Wnt/β-catenin signaling pathway that are activated by β-catenin binding. Now a Xenopus ventral specific transcription factor Xom has also been identified to bear transactivation activity by binding to Lef/Tcf factors [1].展开更多
文摘LEF1/TCFs are high mobility group box-containing transcriptional factors mediating canonical Wnt/β-catenin signaling during early embryogenesis and tumorigenesis. β-Catenin forms a complex with LEF 1/TCFs and transactivates LEF1/TCF-mediated transcriptions during dorsalization. Although LEF-mediated transcription is also implicated in ventralization, the underlying molecular mechanism is not well understood. Using the vertebrate Xenopus laevis model system, we found that Xom, which is a ventralizing homeobox protein with dual roles of transcriptional activation and repression, forms a complex with LEF 1/TCF through its homeodomain and transactivates LEF 1/TCF-mediated transcription through its N-terminal transactivation domain （TAD）. Our data show that Xom lacking the N-terminal TAD fails to transactivate ventral genes, such as BMP4 and Xom itself, but retains the ability to suppress transcriptional activation of dorsal gene promoters, such as the Goosecoid promoter, indicating that transactivation and repression are separable functions of Xom. It has been postulated that Xom forms a positive re-enforcement loop with BMP4 to promote ventral- ization and to suppress dorsal gene expression. Consistent with an essential role of Xom transactivation of LEF1/TCFs during early embryogenesis, we found that expression of the dominant-negative Xom mutant that lacks the TAD fails to re-enforce the ventral signaling of BMP4 and causes a catastrophic effect during gastrulation. Our data suggest that the functional interaction of Xom and LEF 1/TCF-factors is essential for ventral cell fate determination and that LEF 1/TCF factors may function as a point of convergence to mediate the combined signaling of Wnt/β-catenin and BMP4/Xom pathways during early embryogenesis.
文摘Both the Wnt/β-catenin and Bone morphogenetic protein （Bmp） signaling pathways play critical roles in dorsal-ventral patterning of the Xenopus embryos. The lymphoid enhancer binding factor （Lef） / T cell factor （Tcf） have been viewed as dedicated transcription factors of the Wnt/β-catenin signaling pathway that are activated by β-catenin binding. Now a Xenopus ventral specific transcription factor Xom has also been identified to bear transactivation activity by binding to Lef/Tcf factors [1].
