MADR2 maps to 18q21 and encodes a TGF beta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma
MADR2 maps to 18q21 and encodes a TGF beta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma
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DOI：
10.1016/s0092-8674(00)80128-2
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发表时间：
1996-08-23
期刊：
影响因子：
64.5
通讯作者：
Attisano, L
中科院分区：
文献类型：
--
作者：
Eppert, K;Scherer, SW;Attisano, L
MAD相关（MADR）蛋白家族是转化生长因子β（TGF -β）超家族的丝氨酸/苏氨酸激酶受体信号通路的重要组成部分。我们证明MADR2受TGF -β特异性调控，而不受骨形态发生蛋白调控。发现MADR2基因位于18号染色体q21区，靠近DPC4，DPC4是另一种与胰腺癌有关的MADR蛋白。对散发性肿瘤中MADR2的突变分析在结直肠癌中鉴定出4个错义突变，其中2个显示杂合性缺失。对其中3个突变的生化和功能分析表明这些突变是失活的。这些发现表明MADR2是一种肿瘤抑制因子，在结直肠癌中获得的突变可能会破坏TGF -β信号传导。
The MAD-related (MADR) family of proteins are essential components in the signaling pathways of serine/threonine kinase receptors for the transforming growth factor beta (TGF beta) superfamily. We demonstrate that MADR2 is specifically regulated by TGF beta and not bone morphogenetic proteins. The gene for MADR2 was found to reside on chromosome 18q21, near DPC4, another MADR protein implicated in pancreatic cancer. Mutational analysis of MADR2 in sporadic tumors identified four missense mutations in colorectal carcinomas, two of which display a loss of heterozygosity. Biochemical and functional analysis of three of these demonstrates that the mutations are inactivating. These findings suggest that MADR2 is a tumor suppressor and that mutations acquired in colorectal carcinomas may function to disrupt TGF beta signaling.