Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins
Telosome, a mammalian telomere-associated complex formed by multiple telomeric proteins
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DOI：
10.1074/jbc.m409293200
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发表时间：
2004-12-03
影响因子：
4.8
通讯作者：
Songyang, Z
中科院分区：
文献类型：
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作者：
Liu, D;O'Connor, MS;Songyang, Z
在哺乳动物细胞中，端粒结合蛋白TRF1和TRF2在端粒生物学中起着至关重要的作用。它们与其他几种端粒调节因子相互作用，包括TIN 2，PTOP，POT1和RAP 1，以确保端粒的正确维护。TRF1和TRF2被认为发挥不同的功能。TRF1与TIN 2、PTOP和POT1形成复合物并调节端粒长度，而TRF2介导t环形成和末端保护。然而，TRF1和TRF2复合物之间是否发生串扰以及来自这些复合物的信号如何整合用于端粒维持仍有待阐明。通过凝胶过滤和免疫共沉淀实验，我们发现TRF1和TRF2实际上是端粒相关的高分子量复合物（端粒体）的亚基，该复合物还包含POT1，PTOP，RAP 1和TIN 2。我们证明了TRF1相互作用蛋白TIN 2在体内直接结合TRF2，从而将TRF2桥接到TRF1。与这种多蛋白质端粒体模型一致，通过表达端锚聚合酶将TRF1从端粒上剥离不仅减少了TIN 2的端粒募集，还减少了TRF2的端粒募集。这些结果有助于统一以前的观察，并建议端粒的维护依赖于多亚基端体。
In mammalian cells, telomere-binding proteins TRF1 and TRF2 play crucial roles in telomere biology. They interact with several other telomere regulators including TIN2, PTOP, POT1, and RAP1 to ensure proper maintenance of telomeres. TRF1 and TRF2 are believed to exert distinct functions. TRF1 forms a complex with TIN2, PTOP, and POT1 and regulates telomere length, whereas TRF2 mediates t-loop formation and end protection. However, whether cross-talk occurs between the TRF1 and TRF2 complexes and how the signals from these complexes are integrated for telomere maintenance remain to be elucidated. Through gel filtration and co-immunoprecipitation experiments, we found that TRF1 and TRF2 are in fact subunits of a telomere-associated high molecular weight complex (telosome) that also contains POT1, PTOP, RAP1, and TIN2. We demonstrated that the TRF1-interacting protein TIN2 binds TRF2 directly and in vivo, thereby bridging TRF2 to TRF1. Consistent with this multi-protein telosome model, stripping TRF1 off the telomeres by expressing tankyrase reduced telomere recruitment of not only TIN2 but also TRF2. These results help to unify previous observations and suggest that telomere maintenance depends on the multi-subunit telosome.