Gromova I, Biersack H, Jensen S, Nielsen O F, Westergaard O, Andersen A H
Department of Molecular and Structural Biology, University of Aarhus, Denmark.
Biochemistry. 1998 Nov 24;37(47):16645-52. doi: 10.1021/bi981391l.
In mammalian cells, DNA topoisomerase II is the product of two distinct genes encoding the alpha and beta isoforms of the enzyme. Besides homodimeric topoisomerase IIalpha and IIbeta, we have recently shown that alpha/beta heterodimers constitute a third population of topoisomerase II in HeLa cells. We found that topoisomerase II heterodimers are not restricted to HeLa cells but exist in different mammalian cell types, and up to 25% of the total topoisomerase IIbeta population is involved in heterodimer formation. Studies of topoisomerase II phosphorylation in HeLa cells show that heterodimers are phosphorylated in vivo to a significantly lower level compared to homodimeric alpha enzymes, but in contrast to the latter neither heterodimers nor topoisomerase IIbeta homodimers coprecipitate together with a kinase activity that is able to mediate their phosphorylation. However, both enzymes can still be phosphorylated by exogenously added casein kinase II. The differential phosphorylation of topoisomerase II heterodimers suggests an alternative regulation of this topoisomerase II subclass compared to the homodimeric topoisomerase IIalpha counterparts.
在哺乳动物细胞中，DNA拓扑异构酶II是由两个不同基因编码的该酶的α和β同工型的产物。除了同二聚体拓扑异构酶IIα和IIβ外，我们最近还表明，α/β异二聚体构成了HeLa细胞中拓扑异构酶II的第三种类型。我们发现拓扑异构酶II异二聚体并不局限于HeLa细胞，而是存在于不同的哺乳动物细胞类型中，并且总拓扑异构酶IIβ群体中高达25%参与了异二聚体的形成。对HeLa细胞中拓扑异构酶II磷酸化的研究表明，与同二聚体α酶相比，异二聚体在体内的磷酸化水平显著较低，但与后者不同的是，异二聚体和拓扑异构酶IIβ同二聚体都不会与能够介导其磷酸化的激酶活性一起共沉淀。然而，这两种酶仍然可以被外源添加的酪蛋白激酶II磷酸化。拓扑异构酶II异二聚体的差异磷酸化表明，与同二聚体拓扑异构酶IIα对应物相比，这种拓扑异构酶II亚类存在另一种调节方式。
