结肠腺瘤性息肉病蛋白通过与SMAP/KAP3相互作用与微管结合
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国家重点基础研究发展规划(973)项目(G1998051002),国家自然科学基金资助项目(39970372)和国家杰出青年科学基金(39928016).


APC Binds to Microtubules Through The Interaction of SMAP/KAP3
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This work was supported by grants from The Special Funds for Major State Basic Research of China(G1998051002),The National Natural Sciences Foundation of China(39970372) and Youth Fund of National Science Foundation of China(39928016).

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    摘要:

    结肠腺瘤性息肉病基因(adenomatous polyposis coli,APC)的突变导致家族性结肠息肉腺瘤病和散发性结肠癌,APC基因编码一个具有多个结构域、多种磷酸化状态的大分子蛋白质.APC蛋白可通过C段直接或间接与微管结合,同时还可以通过中段与微管结合,但其结合的机制目前还不清楚.为进一步研究APC与其他蛋白质的相互作用,利用酵母双杂交技术运用APC中段(1 500 bp~4 800 bp)构建诱饵质粒,筛选人胎脑cDNA文库,得到一个与APC相互作用的蛋白SMAP/KAP3,SMAP/KAP3是驱动蛋白KIF3A/3B的相关蛋白.通过免疫共沉淀和双色免疫荧光共定位的方法,证实了APC与SMAP/KAP3在体内的相互作用,提示APC可能通过SMAP/KAP3-KIF3A/B参与沿微管的运动.

    Abstract:

    Mutations in the adenomatous polyposis coli(APC) gene are responsible for familial adenomatous polyposis coli(FAP) and sporadic colorectal tumours. APC gene encodes a protein with multiple function domains and different phosphorylation states. APC is involved in regulating cell adherin,migration,prolification,through its interation with multiple proteins.APC binds to microtubles with its C terminal region directly and indirectly, but APC' middle region could also bind to microtubles,but the mechanism is still unclear.For further studying the interactions of APC and other proteins, using the middle fragment of APC(1 500 bp~4 800 bp)as bait, through yeast two-hybrid technology screen the human fetal brain cDNA library, got a novel APC binding protein SMAP/KAP3,and then generated the SMAP/KAP3 antiserum and the flowing coimmunoprecipitation and coimmunofluoresce staining identificated the interaction of APC and SMAP/KAP3.This suggested that the APC utilize the SMAP/KAP3-KIF3A-KIF3B as a motor protein move along the microtubles.

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王成,郑多,钟向阳,夏昆,黄亮群,戴和平,陈玉祥,夏家辉.结肠腺瘤性息肉病蛋白通过与SMAP/KAP3相互作用与微管结合[J].生物化学与生物物理进展,2002,29(6):885-890

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  • 收稿日期:2002-06-05
  • 最后修改日期:2002-06-20
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