Shetty Premnath, Lo Miao-Chia, Robertson Scott M, Lin Rueyling
Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
Dev Biol. 2005 Sep 15;285(2):584-92. doi: 10.1016/j.ydbio.2005.07.008.
Canonical Wnt signaling converts the TCF/LEF transcription factor from repressor to activator by increasing nuclear levels of its coactivator, beta-catenin. A striking exception had been reported for Wnt-induced endoderm formation during C. elegans embryogenesis. It has long been believed that transcriptional activation of Wnt target genes in the endoderm precursor occurred due to a lowering of nuclear levels of the worm TCF/LEF protein, POP-1, effectively alleviating POP-1 repressive activity. Contrary to this model, we demonstrate here that POP-1 directly activates Wnt target genes in the endoderm precursor. Wnt converts POP-1 from a repressor to an activator, and this conversion requires that POP-1 nuclear levels be lowered in the endoderm precursor. We propose that the balance between TCF/LEF and coactivator(s), achieved by elevating coactivator levels (the canonical pathway) and/or reducing TCF/LEF levels (worm endoderm), determines Wnt signal strength.
经典Wnt信号通路通过增加其共激活因子β-连环蛋白的核水平，将TCF/LEF转录因子从阻遏物转变为激活物。在秀丽隐杆线虫胚胎发生过程中，Wnt诱导内胚层形成有一个显著的例外情况被报道。长期以来，人们一直认为内胚层前体中Wnt靶基因的转录激活是由于线虫TCF/LEF蛋白POP-1的核水平降低，从而有效减轻了POP-1的抑制活性。与该模型相反，我们在此证明POP-1在内胚层前体中直接激活Wnt靶基因。Wnt将POP-1从阻遏物转变为激活物，而这种转变要求内胚层前体中POP-1的核水平降低。我们提出，通过提高共激活因子水平（经典途径）和/或降低TCF/LEF水平（线虫内胚层）实现的TCF/LEF与共激活因子之间的平衡决定了Wnt信号强度。
