MADR2定位于18号染色体长臂21区，编码一种受转化生长因子β调控的MAD相关蛋白，该蛋白在结肠直肠癌中发生功能突变。
MADR2 maps to 18q21 and encodes a TGFbeta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma.
作者信息
Eppert K, Scherer S W, Ozcelik H, Pirone R, Hoodless P, Kim H, Tsui L C, Bapat B, Gallinger S, Andrulis I L, Thomsen G H, Wrana J L, Attisano L
机构信息
Division of Gastroenterology, The Hospital for Sick Children, Toronto, Ontario, Canada.
出版信息
Cell. 1996 Aug 23;86(4):543-52. doi: 10.1016/s0092-8674(00)80128-2.
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 (TGFbeta) superfamily. We demonstrate that MADR2 is specifically regulated by TGFbeta 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 TGFbeta signaling.
MAD相关（MADR）蛋白家族是转化生长因子β（TGFβ）超家族丝氨酸/苏氨酸激酶受体信号通路中的重要组成部分。我们证明MADR2受TGFβ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是另一种与胰腺癌相关的MADR蛋白。对散发性肿瘤中MADR2的突变分析发现，结直肠癌中有四个错义突变，其中两个表现为杂合性缺失。对其中三个突变进行的生化和功能分析表明这些突变具有失活作用。这些发现提示MADR2是一种肿瘤抑制因子，结直肠癌中获得的突变可能会破坏TGFβ信号传导。
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