Molecular Distinctions between Aurora A and B: A Single Residue Change Transforms Aurora A into Correctly Localized and Functional Aurora B
Molecular Distinctions between Aurora A and B: A Single Residue Change Transforms Aurora A into Correctly Localized and Functional Aurora B
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DOI：
10.1091/mbc.e09-05-0370
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发表时间：
2009-08-01
影响因子：
3.3
通讯作者：
Margolis, Robert L.
中科院分区：
文献类型：
--
作者：
Hans, Fabienne;Skoufias, Dimitrios A.;Margolis, Robert L.
Aurora A和Aurora B是副有丝分裂激酶，具有高度相似的一级序列。两者都对有丝分裂进程很重要，但它们的定位和功能不同。我们将shRNA抑制与Aurora突变体的过表达相结合，以解决Aurora A和Aurora B之间差异的原因。Aurora A残基甘氨酸198（G198）突变为天冬酰胺以模拟Aurora B的对齐天冬酰胺142（N142），导致Aurora A结合Aurora B结合配偶体INCENP，但不结合Aurora A结合配偶体TPX 2。突变体Aurora A挽救了Aurora B的有丝分裂功能。我们的结论是，结合INCENP是唯一的极光B的独特功能的关键。尽管Aurora A的G198是TPX 2结合所必需的，但N142 G Aurora B保留了INCENP结合和Aurora B功能。因此，尽管单个残基变化转化了Aurora A，但Aurora B的相互突变并不产生Aurora A功能。Aurora A-Delta 120 N-末端截短构建体增强了Aurora A与Aurora B的相似性，因为它不与中心体相关，而是与动粒相关。
Aurora A and Aurora B, paralogue mitotic kinases, share highly similar primary sequence. Both are important to mitotic progression, but their localizations and functions are distinct. We have combined shRNA suppression with overexpression of Aurora mutants to address the cause of the distinction between Aurora A and Aurora B. Aurora A residue glycine 198 (G198), mutated to asparagine to mimic the aligned asparagine 142 (N142) of Aurora B, causes Aurora A to bind the Aurora B binding partner INCENP but not the Aurora A binding partner TPX2. The mutant Aurora A rescues Aurora B mitotic function. We conclude that binding to INCENP is alone critical to the distinct function of Aurora B. Although G198 of Aurora A is required for TPX2 binding, N142G Aurora B retains INCENP binding and Aurora B function. Thus, although a single residue change transforms Aurora A, the reciprocal mutation of Aurora B does not create Aurora A function. An Aurora A-Delta 120 N-terminal truncation construct reinforces Aurora A similarity to Aurora B, because it does not associate with centrosomes but instead associates with kinetochores.