Gentili Christian, Castor Dennis, Kaden Svenja, Lauterbach David, Gysi Mario, Steigemann Patrick, Gerlich Daniel W, Jiricny Josef, Ferrari Stefano
Institute of Molecular Cancer Research of the University of Zurich and the ETH Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
Institute of Biochemistry, Schafmattstrasse 18, HPM E17.2, Swiss Institute of Technology Zurich (ETHZ), CH-8093, Zurich, Switzerland.
PLoS One. 2015 Jul 22;10(7):e0133576. doi: 10.1371/journal.pone.0133576. eCollection 2015.
RUVBL1 (RuvB-like1) and RUVBL2 (RuvB-like 2) are integral components of multisubunit protein complexes involved in processes ranging from cellular metabolism, transcription and chromatin remodeling to DNA repair. Here, we show that although RUVBL1 and RUVBL2 are known to form heterodimeric complexes in which they stabilize each other, the subunits separate during cytokinesis. In anaphase-to-telophase transition, RUVBL1 localizes to structures of the mitotic spindle apparatus, where it partially co-localizes with polo-like kinase 1 (PLK1). The ability of PLK1 to phosphorylate RUVBL1-but not RUVBL2-in vitro and their physical association in vivo suggest that this kinase differentially regulates the function of the RuvB-like proteins during mitosis. We further show that siRNA-mediated knock-down of RuvB-like proteins causes severe defects in chromosome alignment and segregation. In addition, we show that the ATPase activity of RUVBL1 is indispensable for cell proliferation. Our data thus demonstrate that RUVBL1 is essential for efficient mitosis and proliferation.
RUVBL1（类RuvB1）和RUVBL2（类RuvB2）是多亚基蛋白复合物的组成成分，参与从细胞代谢、转录、染色质重塑到DNA修复等一系列过程。在此，我们发现，尽管已知RUVBL1和RUVBL2形成异源二聚体复合物并相互稳定，但在胞质分裂过程中这些亚基会分离。在后期到末期的转变过程中，RUVBL1定位于有丝分裂纺锤体装置的结构上，在那里它与polo样激酶1（PLK1）部分共定位。PLK1在体外磷酸化RUVBL1（而非RUVBL2）的能力以及它们在体内的物理关联表明，这种激酶在有丝分裂过程中对类RuvB蛋白的功能进行差异性调节。我们进一步表明，小干扰RNA介导的类RuvB蛋白敲低会导致染色体排列和分离出现严重缺陷。此外，我们表明RUVBL1的ATP酶活性对细胞增殖不可或缺。因此，我们的数据证明RUVBL1对高效有丝分裂和增殖至关重要。
