Im Jongmi, Kim Hanjun, Kim Sewoon, Jho Eek-Hoon
Department of Life Science, The University of Seoul, 90 Jeonnong-dong, Dongdaemun-gu, Seoul 130-743, Korea.
Biochem Biophys Res Commun. 2007 Mar 2;354(1):296-301. doi: 10.1016/j.bbrc.2006.12.205. Epub 2007 Jan 8.
To identify novel target genes regulated by Wnt/beta-catenin signaling, microarray analysis was performed with L929 fibroblast cells. In this report, we show that the expression of PRDC (Protein Related to DAN and Cerberus), previously known as an antagonist of Nodal, BMP (bone morphogenetic protein), and Wnt signals, is specifically induced by Wnt/beta-catenin signaling, and also show that the transcriptional activation is mediated in a Tcf/LEF-independent manner. The PRDC induced by Wnt/beta-catenin does not inhibit Wnt signaling, but does inhibit BMP-4 signaling. The inhibition of BMP-4-induced reporter activity by the treatment of conditioned media from beta-catenin(S37A)-expressing cells suggests that the PRDC induced by beta-catenin is secreted outside of cells and antagonizes BMP-4 signaling. We propose that PRDC might serve as a mediator to antagonize BMP-4 signaling by Wnt.
为了鉴定受Wnt/β-连环蛋白信号通路调控的新靶基因，我们对L929成纤维细胞进行了微阵列分析。在本报告中，我们发现PRDC（与DAN和Cerberus相关的蛋白质）的表达，该蛋白先前被认为是Nodal、骨形态发生蛋白（BMP）和Wnt信号的拮抗剂，可被Wnt/β-连环蛋白信号通路特异性诱导，并且还表明转录激活是以不依赖Tcf/LEF的方式介导的。由Wnt/β-连环蛋白诱导的PRDC并不抑制Wnt信号通路，但确实抑制BMP-4信号通路。用表达β-连环蛋白（S37A）的细胞的条件培养基处理可抑制BMP-4诱导的报告基因活性，这表明由β-连环蛋白诱导的PRDC分泌到细胞外并拮抗BMP-4信号通路。我们提出PRDC可能作为一种介质，通过Wnt拮抗BMP-4信号通路。
