The 'destruction box' of cyclin A allows B-type cyclins to be ubiquitinated, but not efficiently destroyed
The 'destruction box' of cyclin A allows B-type cyclins to be ubiquitinated, but not efficiently destroyed
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DOI：
10.1002/j.1460-2075.1996.tb00668.x
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发表时间：
1996-06-17
期刊：
影响因子：
11.4
通讯作者：
Hunt, T
中科院分区：
文献类型：
--
作者：
Klotzbucher, A;Stewart, E;Hunt, T
在有丝分裂末期，有丝分裂细胞周期蛋白的程序性蛋白水解破坏是细胞周期调控中的一个重要环节。这种蛋白水解依赖于一个由9个氨基酸残基组成的保守基序，称为“破坏盒”，它位于离N端40-50个氨基酸残基处。然而，当细胞周期蛋白A型破坏盒取代细胞周期蛋白B1或B2中的正常破坏盒时，所得到的构建体出乎意料地稳定，尽管细胞周期蛋白A中B型破坏盒的匡威取代允许正常降解。我们比较了各种细胞周期蛋白构建体的泛素化，并发现尽管破坏盒中高度保守残基的突变强烈降低了泛素化中间体的水平，稳定的破坏盒“交换”构建体确实形成了这样的加合物，因此，虽然泛素化可能是细胞周期蛋白破坏所必需的，但它是不够的。我们还发现多泛素化的细胞周期蛋白衍生物仍然与p34（cdc 2）结合，而p34本身并没有被检测到泛素化，这就提出了细胞周期蛋白和cdc 2在降解过程中是如何彼此解离的，以及在什么阶段解离的问题。
The destruction of mitotic cyclins by programmed proteolysis at the end of mitosis is an important element in cell cycle control, This proteolysis depends on a conserved motif of nine residues known as the 'destruction box', which is located 40-50 residues from the N-terminus, The sequences of the A- and B-type destruction boxes are slightly different, which might account for the differences in timing of their destruction. When the cyclin A-type destruction box was substituted for the normal one in cyclin B1 or B2, however, the resulting constructs were unexpectedly stable, although the converse substitution of B-type destruction boxes in cyclin A permitted normal degradation, We compared the ubiquitination of various cyclin constructs, and found that whereas mutation of the highly conserved residues in the destruction box strongly reduced the level of ubiquitinated intermediates, the stable destruction box 'swap' constructs did form such adducts, Thus, while ubiquitination is probably necessary for cyclin destruction, it is not sufficient. We also found that poly-ubiquitinated cyclin derivatives are still bound to p34(cdc2), which is not detectably ubiquitinated itself, raising the questions of how cyclin and cdc2 dissociate from one another, and at what stage, in the process of degradation.