Interaction between RB protein and NuMA is required for proper alignment of spindle microtubules
Interaction between RB protein and NuMA is required for proper alignment of spindle microtubules
复制标题
RB 蛋白和 NuMA 之间的相互作用是纺锤体微管正确排列所必需的
作者：
Uchida;C.;Hattori;T.;Takahashi;H.;Yamamoto;N.;Kitagawa;M. and Taya;Y.
视网膜母细胞瘤蛋白（pRB）通过与细胞蛋白质相互作用控制细胞周期进程和细胞周期退出。许多pRB结合蛋白在基因转录或染色质结构调节中起作用，在其pRB结合结构域中具有LXCXE基序。在这项研究中，我们发现核有丝分裂器蛋白（NuMA），一种有丝分裂纺锤体组织者，通过位于其C末端区域的LSCEE序列与pRB相互作用。siRNA介导的pRB下调导致有丝分裂细胞中NuMA的异常分布和纺锤体微管的排列。纺锤体微管的异常组织也伴随着过度表达的NuMA突变体（mut-NuMA）与LSGEK突变引起的pRB结合缺陷的不对齐。在2周的培养期间，mut-NuMA-过表达细胞显示出比野生型NuMA（wt-NuMA）-过表达细胞更低的存活效力。有趣的是，pRB的敲低在2周后将wt-NuMA-过表达细胞的群体减少到与mut-NuMA细胞相同的水平。两者合计，pRB可能有一个新的功能，调节有丝分裂功能的NuMA和纺锤体组织，这是必要的适当的细胞周期进程。
Retinoblastoma protein (pRB) controls cell cycle progression and cell cycle exit through interactions with cellular proteins. Many pRB‐binding proteins, which function in gene transcription or modulation of chromatin structure, harbor LXCXE motifs in their binding domain for pRB. In this study, we found that nuclear mitotic apparatus protein (NuMA), a mitotic spindle organizer, interacts with pRB through LSCEE sequences located in its C‐terminal region. siRNA‐mediated down‐regulation of pRB caused aberrant distribution of NuMA and alignment of spindle microtubules in mitotic cells. Abnormal organization of spindle microtubules was also accompanied by misalignment of an over‐expressed NuMA mutant (mut‐NuMA) with a defect in pRB binding caused by an LSGEK mutation. The mut‐NuMA‐over‐expressing cells showed lower potency for survival than wild‐type NuMA (wt‐NuMA)‐over‐expressing cells during 2 weeks of culture. Interestingly, knockdown of pRB reduced the population of wt‐NuMA‐over‐expressing cells to the same level as mut‐NuMA cells after 2 weeks. Taken together, pRB may have a novel function in regulating the mitotic function of NuMA and spindle organization, which are required for proper cell cycle progression.