Wehman Ann M, Staub Wendy, Baier Herwig
Programs in Genetics and Developmental Biology, University of California-San Francisco, 1550 4th Street, San Francisco, CA 94158-2722, USA.
Dev Biol. 2007 Mar 1;303(1):144-56. doi: 10.1016/j.ydbio.2006.10.043. Epub 2006 Nov 3.
The anaphase-promoting complex/cyclosome (APC/C) regulates multiple stages of the cell cycle, most prominently mitosis. We describe zebrafish with mutations in two APC/C subunits, Cdc16 and Cdc26, whose phenotypes reveal a multifaceted set of defects resulting from the gradual depletion of the APC/C. First, loss of the APC/C in dividing cells results in mitotic arrest, followed by apoptosis. This defect becomes detectable in different organs at different larval ages, because the subunits of the APC/C are maternally deposited, are unusually stable, and are depleted at uneven rates in different tissues. Second, loss of the APC/C in quiescent or differentiated cells results in improper re-entry into the cell cycle, again in an apparently tissue-specific manner. This study is the first demonstration of both functions of the APC/C in a vertebrate organism and also provides an illustration of the surprisingly complex effects that essential, maternally supplied factors can have on the growing animal over a period of 10 days or longer.
后期促进复合物/细胞周期体(APC/C)调控细胞周期的多个阶段,其中最显著的是有丝分裂。我们描述了斑马鱼中两个APC/C亚基Cdc16和Cdc26发生突变的情况,其表型揭示了由于APC/C逐渐耗竭而导致的一系列多方面的缺陷。首先,分裂细胞中APC/C的缺失会导致有丝分裂停滞,随后发生凋亡。这种缺陷在不同幼虫年龄的不同器官中可被检测到,因为APC/C的亚基是母源沉积的,异常稳定,且在不同组织中以不均匀的速率耗竭。其次,静止或分化细胞中APC/C的缺失会导致以明显的组织特异性方式再次不恰当地重新进入细胞周期。这项研究首次证明了APC/C在脊椎动物体内的这两种功能,同时也说明了母源供应的必需因子在长达10天或更长时间内对生长中的动物可能产生的惊人复杂影响。