Tsang William Y, Spektor Alexander, Vijayakumar Sangeetha, Bista Bigyan R, Li Ji, Sanchez Irma, Duensing Stefan, Dynlacht Brian D
Department of Pathology, NYU School of Medicine and Cancer Institute, Smilow Research Building, New York, NY 10016, USA.
Dev Cell. 2009 May;16(5):649-60. doi: 10.1016/j.devcel.2009.03.004.
Centrosomes duplicate only once per cell cycle, but the controls that govern this process are largely unknown. We have identified Cep76, a centriolar protein that interacts with CP110. Cep76 is expressed at low levels in G1 and is induced in S and G2 phase, during which point centrioles have already commenced duplication. Interestingly, depletion of Cep76 drives the accumulation of centriolar intermediates in certain types of cancer cells. Enforced Cep76 expression specifically inhibits centriole amplification in cells undergoing multiple rounds of duplication without preventing the formation of extra procentrioles from a parental template. Furthermore, elevated levels of Cep76 do not affect normal centriole duplication. Thus, Cep76 helps limit duplication to once per cell cycle. Our findings also point to mechanistic differences between normal duplication and aberrant centriole amplification, as well as distinctions between diverse modes of amplification.
中心体在每个细胞周期仅复制一次，但控制这一过程的机制在很大程度上尚不清楚。我们鉴定出了Cep76，一种与CP110相互作用的中心粒蛋白。Cep76在G1期低水平表达，并在S期和G2期被诱导表达，而此时中心粒已经开始复制。有趣的是，Cep76的缺失会促使某些类型癌细胞中中心粒中间体的积累。在经历多轮复制的细胞中，强制表达Cep76可特异性抑制中心粒扩增，但不会阻止从亲代模板形成额外的子中心粒。此外，Cep76水平升高并不影响正常的中心粒复制。因此，Cep76有助于将每个细胞周期的复制限制为一次。我们的研究结果还指出了正常复制与异常中心粒扩增之间的机制差异，以及不同扩增模式之间的区别。
