纺锤体组装检查点失活无法抑制AurA突变型果蝇中的成神经细胞瘤形成。
Spindle assembly checkpoint inactivation fails to suppress neuroblast tumour formation in aurA mutant Drosophila.
作者信息
Caous Renaud, Pascal Aude, Romé Pierre, Richard-Parpaillon Laurent, Karess Roger, Giet Régis
机构信息
Institut de Génétique et Développement de Rennes-Université de Rennes I-CNRS- UMR 6290, 2 avenue du Pr Léon Bernard, 35043 Rennes, France.
Institut Jacques Monod-Université Paris Diderot-Paris 7, 15 rue Hélène Brion, 75205 Paris, France.
出版信息
Nat Commun. 2015 Nov 16;6:8879. doi: 10.1038/ncomms9879.
Tissue homeostasis requires accurate control of cell proliferation, differentiation and chromosome segregation. Drosophila sas-4 and aurA mutants present brain tumours with extra neuroblasts (NBs), defective mitotic spindle assembly and delayed mitosis due to activation of the spindle assembly checkpoint (SAC). Here we inactivate the SAC in aurA and sas-4 mutants to determine whether the generation of aneuploidy compromises NB proliferation. Inactivation of the SAC in the sas-4 mutant impairs NB proliferation and disrupts euploidy. By contrast, disrupting the SAC in the aurA mutant does not prevent NB amplification, tumour formation or chromosome segregation. The monitoring of Mad2 and cyclin B dynamics in live aurA NBs reveals that SAC satisfaction is not coupled to cyclin B degradation. Thus, the NBs of aurA mutants present delayed mitosis, with accurate chromosome segregation occurring in a SAC-independent manner. We report here the existence of an Aurora A-dependent mechanism promoting efficient, timed cyclin B degradation.
组织稳态需要对细胞增殖、分化和染色体分离进行精确控制。果蝇sas-4和aurA突变体表现出脑肿瘤，伴有额外的神经母细胞（NBs），有丝分裂纺锤体组装缺陷，并且由于纺锤体组装检查点（SAC）的激活导致有丝分裂延迟。在这里，我们使aurA和sas-4突变体中的SAC失活，以确定非整倍体的产生是否会损害NB增殖。sas-4突变体中SAC的失活会损害NB增殖并破坏整倍性。相比之下，在aurA突变体中破坏SAC并不能阻止NB扩增、肿瘤形成或染色体分离。对活的aurA NB中Mad2和细胞周期蛋白B动态的监测表明，SAC的满足与细胞周期蛋白B的降解没有关联。因此，aurA突变体的NB表现出有丝分裂延迟，精确的染色体分离以不依赖SAC的方式发生。我们在此报告存在一种依赖极光激酶A的机制，该机制促进高效、定时的细胞周期蛋白B降解。
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