The APC-associated protein EB1 associates with components of the dynactin complex and cytoplasmic dynein intermediate chain
The APC-associated protein EB1 associates with components of the dynactin complex and cytoplasmic dynein intermediate chain
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DOI：
10.1016/s0960-9822(99)80190-0
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发表时间：
1999-04-22
期刊：
影响因子：
9.2
通讯作者：
Bierer, BE
中科院分区：
文献类型：
--
作者：
Berrueta, L;Tirnauer, JS;Bierer, BE
人EB1是一种高度保守的蛋白，它与人腺瘤性息肉病（APC）肿瘤抑制蛋白[1]的羧基端结合，这是APC的一个结构域，在结直肠癌[2]中通常被删除。EB1属于一个微管相关蛋白家族，包括裂糖酵母pombe Mal3[3]和酿酒酵母Bim1p [4]， Bim1p似乎通过与酵母动力蛋白复合物[5]的组成部分Act5的遗传相互作用来调节细胞分裂的时间，而酵母动力蛋白复合物的主要功能似乎是定位有丝分裂纺锤体[6]，在动物细胞中，动力蛋白已被证明在多种过程中起作用。包括细胞器运输，有丝分裂纺锤体的形成，可能还有细胞分裂[7-10]。在这里，我们证明了人类EB1可以与p150（glue）共沉淀，p150是动力蛋白复合物的一种成员。EB1也被发现与胞质动力蛋白（CDIC）的中间链和动力蛋白（p50）相关，动力蛋白是动力蛋白复合体的另一个组成部分，但与动力蛋白重链无关，在一个蔗糖密度梯度约5S的复合体中沉积。EB1与dynactin复合物成员的结合是独立于APC的，并且在没有完整的微管细胞骨架的情况下被保存下来。EB1与dynactin复合物成员和CDIC的分子相互作用可能对微管过程很重要。
Human EB1 is a highly conserved protein that binds to the carboxyl terminus of the human adenomatous polyposis coli (APC) tumor suppressor protein [1], a domain of APC that is commonly deleted in colorectal neoplasia [2]. EB1 belongs to a family of microtubule-associated proteins that includes Schizosaccharomyces pombe Mal3 [3] and Saccharomyces cerevisiae Bim1p [4], Bim1p appears to regulate the timing of cytokinesis as demonstrated by a genetic interaction with Act5, a component of the yeast dynactin complex [5], Whereas the predominant function of the dynactin complex in yeast appears to be in positioning the mitotic spindle [6], in animal cells, dynactin has been shown to function in diverse processes, including organelle transport, formation of the mitotic spindle, and perhaps cytokinesis [7-10], Here, we demonstrate that human EB1 can be coprecipitated with p150(Glued), a member of the dynactin protein complex. EB1 was also found associated with the intermediate chain of cytoplasmic dynein (CDIC) and with dynamitin (p50), another component of the dynactin complex, but not with dynein heavy chain, in a complex that sedimented at approximately 5S in a sucrose density gradient. The association of EB1 with members of the dynactin complex was independent of APC and was preserved in the absence of an intact microtubule cytoskeleton, The molecular interaction of EB1 with members of the dynactin complex and with CDIC may be important for microtubule-based processes.