Tankyrase‐1 assembly to large protein complexes blocks its telomeric function
Tankyrase‐1 assembly to large protein complexes blocks its telomeric function
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DOI：
10.1016/j.febslet.2010.07.062
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发表时间：
2010-09
期刊：
影响因子：
3.5
通讯作者：
Kaori Hatsugai;T. Ohishi;Y. Sugimoto;H. Seimiya
中科院分区：
文献类型：
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作者：
Kaori Hatsugai;T. Ohishi;Y. Sugimoto;H. Seimiya
tankyase -1 poly（ADP-ribosyl）控制端粒结合蛋白TRF1。这种翻译后修饰将TRF1与端粒分离，增强端粒酶介导的端粒延伸。tankyase -1通过其不育的α基序结构域进行多聚，但其功能含义仍然难以捉摸。在这里，我们发现过量的tankyase -1形成点状核灶。这种焦点的形成既取决于亲同性的多聚作用，也取决于亲异性的蛋白质相互作用。这些病灶处于功能休眠状态，因为它们不能有效地从端粒释放TRF1。一直以来，tankyase -1的过度表达削弱了其延长端粒的能力。这些观察结果表明，tankyase -1组装成大的蛋白质复合物掩盖了它的端粒功能。结构摘要：MINT-7987689， MINT-7987677: tankyase -1 （uniprotkb:O95271）和TRF1 （uniprotkb:P54274）共定位（MI:0403）通过荧光显微镜（MI:0416） MINT-7987977: tankyase -1 （uniprotkb:O95271）通过抗标签共免疫沉淀（MI:0007）与TRF1 （uniprotkb:P54274）物理相互作用（MI:0915） MINT-7987998: tankyase -1 （uniprotkb:O95271）通过抗标签共免疫沉淀（MI:0007）与tankyase -1 （uniprotkb:O95271）物理相互作用（MI:0915）
Tankyrase-1 poly(ADP-ribosyl)ates the telomere-binding protein TRF1. This post-translational modification dissociates TRF1 from telomeres, enhancing telomerase-mediated telomere elongation. Tankyrase-1 multimerizes via its sterile alpha motif domain, but its functional implication remains elusive. Here, we found that excessive amounts of tankyrase-1 form punctate nuclear foci. This focus formation depends on both homophilic multimerization and heterophilic protein–protein interaction. These foci are functionally dormant because they do not efficiently release TRF1 from telomeres. Consistently, hyper-overexpression of tankyrase-1 attenuates its ability to elongate telomeres. These observations suggest that tankyrase-1 assembly to large protein complexes masks its telomeric function. STRUCTURED SUMMARY: MINT-7987689, MINT-7987677: Tankyrase-1 (uniprotkb:O95271) and TRF1 (uniprotkb:P54274) colocalize (MI:0403) by fluorescence microscopy (MI:0416) MINT-7987977: Tankyrase-1 (uniprotkb:O95271) physically interacts (MI:0915) with TRF1 (uniprotkb:P54274) by anti tag coimmunoprecipitation (MI:0007) MINT-7987998: Tankyrase-1 (uniprotkb:O95271) physically interacts (MI:0915) with Tankyrase-1 (uniprotkb:O95271) by anti tag coimmunoprecipitation (MI:0007).