Haataja L, Groffen J, Heisterkamp N
Section of Molecular Carcinogenesis, Department of Pathology, Childrens Hospital Los Angeles Research Institute and University of Southern California School of Medicine, Los Angeles, CA 90027, USA.
Int J Mol Med. 1998 Apr;1(4):665-70. doi: 10.3892/ijmm.1.4.665.
Rac3 is a small GTPase of the Rho family, members of which have been implicated in tumorigenesis, cell growth/death and organization of the actin cytoskeleton. Many Rac-interacting proteins or effectors identified to date have a role in cytoskeletal organization. Using the yeast two-hybrid system, we have isolated a novel Rac3-interacting protein from a human placenta cDNA library which has no homology to other previously identified Rac-interacting proteins. Sequence analysis revealed that this protein is C1D, the human homolog of the murine SUN-CoR protein which acts as a corepressor for the thyroid hormone receptor. In yeast cells, C1D binds to constitutively activated but not to GDP-bound Rac3. When coexpressed with Rac3 in COS cells, C1D complexed with constitutively active Rac3 but not with wild-type Rac3, demonstrating that C1D-Rac3 interactions take place in vivo in mammalian cells and that C1D appears to be an effector of Rac3. The C1D gene was mapped to human chromosome 2, which frequently shows deletions in human follicular thyroid carcinomas.
Rac3是Rho家族的一种小GTP酶，该家族成员与肿瘤发生、细胞生长/死亡及肌动蛋白细胞骨架的组织有关。迄今鉴定出的许多与Rac相互作用的蛋白质或效应器在细胞骨架组织中发挥作用。利用酵母双杂交系统，我们从人胎盘cDNA文库中分离出一种新型的与Rac3相互作用的蛋白质，它与其他先前鉴定的与Rac相互作用的蛋白质没有同源性。序列分析表明，该蛋白质是C1D，即小鼠SUN-CoR蛋白的人类同源物，SUN-CoR蛋白作为甲状腺激素受体的共抑制因子发挥作用。在酵母细胞中，C1D与组成型激活的Rac3结合，但不与结合GDP的Rac3结合。当在COS细胞中与Rac3共表达时，C1D与组成型活性Rac3形成复合物，但不与野生型Rac3形成复合物，这表明C1D-Rac3相互作用在哺乳动物细胞的体内发生，且C1D似乎是Rac3的一种效应器。C1D基因定位于人类2号染色体，该染色体在人类滤泡性甲状腺癌中经常出现缺失。
