Pieroni Stefania, Della Fazia Maria Agnese, Castelli Marilena, Piobbico Danilo, Bartoli Daniela, Brunacci Cinzia, Bellet Marina Maria, Viola-Magni Mariapia, Servillo Giuseppe
Università degli Studi di Perugia, Dipartimento di Medicina Clinica e Sperimentale, Policlinico Monteluce, CEMIN, Perugia, Italy.
Cell Cycle. 2008 May 15;7(10):1462-6. doi: 10.4161/cc.7.10.5882. Epub 2008 Mar 7.
Centrosomes direct microtubule organization during cell division. Aberrant number of centrosomes results from alteration of its components and leads to abnormal mitoses and chromosome instability. HOPS is a newly discovered protein isolated during liver regeneration, implicated in cell proliferation. Here, we provide evidence that HOPS is an integral constituent of centrosomes. HOPS is associated with classical markers of centrosomes and found in cytosolic complexes containing CRM-1, gamma-tubulin, eEF-1A and HSP70. These features suggest that HOPS is involved in centrosome assembly and maintenance. HOPS depletion generates supernumerary centrosomes, multinucleated cells and multipolar spindle formation leading to activation of p53 checkpoint and cell cycle arrest. The presence of HOPS in cytosolic complexes supports that centrosome proteins might be preassembled in the cytoplasm to then be rapidly recruited for centrosome duplication. Altogether these data show HOPS implication in the control of cell division. HOPS contribution appears relevant to understand genomic instability and centrosome amplification in cancer.
中心体在细胞分裂过程中指导微管组织。中心体数量异常是其组成成分改变所致，会导致异常有丝分裂和染色体不稳定。HOPS是在肝脏再生过程中分离出的一种新发现的蛋白质，与细胞增殖有关。在此，我们提供证据表明HOPS是中心体的一个组成部分。HOPS与中心体的经典标志物相关，并存在于含有CRM-1、γ-微管蛋白、eEF-1A和HSP70的胞质复合物中。这些特征表明HOPS参与中心体的组装和维持。HOPS缺失会产生多余的中心体、多核细胞和多极纺锤体形成，导致p53检查点激活和细胞周期停滞。HOPS在胞质复合物中的存在支持中心体蛋白可能在细胞质中预先组装，然后迅速被招募用于中心体复制。这些数据表明HOPS参与细胞分裂的调控。HOPS的作用似乎与理解癌症中的基因组不稳定和中心体扩增相关。
