The tumor suppressor proteins ASPP1 and ASPP2 interact with C-Nap1 and regulate centrosome linker reassembly
The tumor suppressor proteins ASPP1 and ASPP2 interact with C-Nap1 and regulate centrosome linker reassembly
复制标题
肿瘤抑制蛋白 ASPP1 和 ASPP2 与 C-Nap1 相互作用并调节中心体接头重新组装
DOI：
10.1016/j.bbrc.2015.01.136
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发表时间：
2015
影响因子：
3.1
通讯作者：
Zhang PZ
中科院分区：
文献类型：
--
作者：
Zhang Yuanyuan;Wang Yuqi;Wei Youheng;Wumaier Reziya;Shen Suqin;Zhang Pingzhao;Yu Long;Zhang Pingzhao;Ma Jian;Peng Jingtao;Zhang PZ
中心体连接体将间期中心体连接在一起，使它们作为单个微管组织中心发挥作用。中心体连接子在有丝分裂开始时被破坏，以确保及时的中心体分离和双极纺锤体形成，并在有丝分裂结束时重新组装。虽然在有丝分裂早期控制中心体连接体解体的机制已被很好地探索，但很少有人知道连接体随后如何在有丝分裂退出之前重新组装。在这里，我们报告ASPP 1和ASPP 2，两个成员的p53（ASPP）家族的凋亡刺激蛋白，参与中心体连接器的重组。我们发现ASPP 1/2与中心体连接蛋白C-Nap 1相互作用。ASPP 1和ASPP 2的共缺失抑制了C-Nap 1在有丝分裂末期与中心体的重新结合。此外，ASPP 1/2促进了C-Nap 1和PP 1 α之间的相互作用，并且这种相互作用被ASPP 1/2的共缺失显著减弱。ASPP 1/2以PP 1依赖的方式拮抗NEK 2A介导的C-Nap 1 Ser 2417/2421磷酸化。ASPP 1和ASPP 2的共耗竭抑制了有丝分裂末期C-Nap 1（Ser 2417/2421）的去磷酸化。基于这些发现，我们认为ASPP 1/2作为PP 1靶向亚基，在有丝分裂结束时促进C-Nap 1去磷酸化和中心体接头的重组。
Centrosome linker tethers interphase centrosomes together allowing them to function as a single microtubule organization center. The centrosome linker is disrupted at the onset of mitosis to ensure timely centrosome disjunction and bipolar spindle formation and is reassembled at the end of mitosis. While the mechanism controlling centrosome linker disassembly at early mitosis has been well explored, little is known about how the linker is subsequently reassembled before mitotic exit. Here we report that ASPP1 and ASPP2, two members of the apoptosis stimulating proteins of p53 (ASPP) family, are involved in centrosome linker reassembly. We showed that ASPP1/2 interacted with centrosome linker protein C-Nap1. Co-depletion of ASPP1 and ASPP2 inhibited re-association of C-Nap1 with centrosome at the end of mitosis. Moreover, ASPP1/2 facilitated the interaction between C-Nap1 and PP1α, and this interaction was significantly reduced by co-depletion of ASPP1/2. ASPP1/2 antagonized the NEK2A-mediated C-Nap1 Ser2417/2421 phosphorylation in a PP1-dependent manner. Co-depletion of ASPP1 and ASPP2 inhibited dephosphorylation of C-Nap1 (Ser2417/2421) at the end of mitosis. Based on these findings, we propose that ASPP1/2 act as PP1-targeting subunits to facilitate C-Nap1 dephosphorylation and centrosome linker reassembly at the end of mitosis.