Feng H, Zhong W, Punkosdy G, Gu S, Zhou L, Seabolt E K, Kipreos E T
Department of Cellular Biology, University of Georgia, Athens, Georgia 30602, USA.
Nat Cell Biol. 1999 Dec;1(8):486-92. doi: 10.1038/70272.
The human cullin protein CUL-2 functions in a ubiquitin-ligase complex with the von Hippel-Lindau (VHL) tumour suppressor protein. Here we show that, in Caenorhabditis elegans, cul-2 is expressed in proliferating cells and is required at two distinct points in the cell cycle, the G1-to-S-phase transition and mitosis. cul-2 mutant germ cells undergo a G1-phase arrest that correlates with accumulation of CKI-1, a member of the CIP/KIP family of cyclin-dependent-kinase inhibitors. In cul-2 mutant embryos, mitotic chromosomes are unable to condense, leading to unequal DNA segregation, chromosome bridging and the formation of multiple nuclei.
人类E3泛素连接酶CUL-2蛋白与抑癌蛋白希佩尔-林道(VHL)共同作用于泛素连接酶复合体。我们发现,在秀丽隐杆线虫中,cul-2在增殖细胞中表达,且在细胞周期的两个不同阶段发挥作用,即G1期到S期的转换以及有丝分裂期。cul-2突变型生殖细胞会经历G1期阻滞,这与细胞周期蛋白依赖性激酶抑制剂CIP/KIP家族成员CKI-1的积累有关。在cul-2突变型胚胎中,有丝分裂染色体无法浓缩,导致DNA不均等分离、染色体桥接以及多核形成。