Tankyrase 1 regulates centrosome function by controlling CPAP stability
Tankyrase 1 regulates centrosome function by controlling CPAP stability
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DOI：
10.1038/embor.2012.86
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发表时间：
2012-08-01
期刊：
影响因子：
7.7
通讯作者：
Smith, Susan
中科院分区：
文献类型：
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作者：
Kim, Mi Kyung;Dudognon, Charles;Smith, Susan
cpap是一种在原发性小头症中发生突变的基因，它是形成前心孔所必需的。在这里，我们发现CPAP的降解和功能是由聚（adp -核糖）聚合酶罐化酶1控制的。体外和体内CPAP均被贮罐酶1 PARsylated。过表达tankyase 1导致CPAP蛋白酶体降解，阻止中心粒复制，而tankyase 1的缺失稳定G1期的CPAP，产生延长的前中心粒和多极体。tankyase 1仅在G1期定位于中心体，与CPAP降解一致。因此，储罐酶1介导的PARsylation调节细胞周期中的CPAP水平，以限制中心粒伸长并确保中心体正常功能。
CPAP-a gene mutated in primary microcephaly-is required for procentriole formation. Here we show that CPAP degradation and function is controlled by the poly(ADP-ribose) polymerase tankyrase 1. CPAP is PARsylated by tankyrase 1 in vitro and in vivo. Overexpression of tankyrase 1 leads to CPAP proteasomal degradation, preventing centriole duplication, whereas depletion of tankyrase 1 stabilizes CPAP in G1, generating elongated procentrioles and multipolarity. Tankyrase 1 localizes to centrosomes exclusively in G1, coinciding with CPAP degradation. Hence, tankyrase 1-mediated PARsylation regulates CPAP levels during the cell cycle to limit centriole elongation and ensure normal centrosome function.