Wu Jun, Cho Hyekyung P, Rhee David B, Johnson Dabney K, Dunlap John, Liu Yie, Wang Yisong
Biosciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA.
J Cell Biol. 2008 May 5;181(3):475-83. doi: 10.1083/jcb.200710127.
Centrosome duplication is tightly controlled in coordination with DNA replication. The molecular mechanism of centrosome duplication remains unclear. Previous studies found that a fraction of human proline-directed phosphatase Cdc14B associates with centrosomes. However, Cdc14B's involvement in centrosome cycle control has never been explored. Here, we show that depletion of Cdc14B by RNA interference leads to centriole amplification in both HeLa and normal human fibroblast BJ and MRC-5 cells. Induction of Cdc14B expression through a regulatable promoter significantly attenuates centriole amplification in prolonged S phase-arrested cells and proteasome inhibitor Z-L(3)VS-treated cells. This inhibitory function requires centriole-associated Cdc14B catalytic activity. Together, these results suggest a potential function for Cdc14B phosphatase in maintaining the fidelity of centrosome duplication cycle.
中心体复制与DNA复制协同受到严格控制。中心体复制的分子机制仍不清楚。先前的研究发现，一部分人源脯氨酸定向磷酸酶Cdc14B与中心体相关联。然而，Cdc14B在中心体周期控制中的作用从未被探究过。在此，我们表明，通过RNA干扰耗尽Cdc14B会导致HeLa细胞以及正常人成纤维细胞BJ和MRC-5细胞中的中心粒扩增。通过可调节启动子诱导Cdc14B表达可显著减弱长期处于S期停滞的细胞和蛋白酶体抑制剂Z-L(3)VS处理的细胞中的中心粒扩增。这种抑制功能需要与中心粒相关的Cdc14B催化活性。总之，这些结果表明Cdc14B磷酸酶在维持中心体复制周期的保真度方面具有潜在功能。
