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首页> 外文期刊>Cell cycle >Clb2 and the APC/C(Cdh1) regulate Swe1 stability.
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Clb2 and the APC/C(Cdh1) regulate Swe1 stability.

机译：Clb2和APC / C（Cdh1）调节Swe1稳定性。

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Swe1/Wee1 regulates mitotic entry by inhibiting Clb2-Cdk1 and its accumulation is involved in stress induced G(2) arrest. The APC/C(Cdh1) substrates Cdc5, Clb2 and Hsl1 regulate Swe1 degradation. We observed that clb2Deltacdh1Delta double mutant S. cerevisiae does not express any detectable levels of Swe1, presumably due to its constitutive degradation. This effect of Cdh1 inactivation is due to stabilization of Cdc5 and Hsl1, as expression of the non-degradable Cdc5(T29A) in clb2Delta cells prevented Swe1 accumulation. Strikingly, expression of non-degradable Hsl1(mdb/mkb) prevented Swe1 accumulation even in wild type Clb2 cells. Interestingly Swe1 accumulation could be reconstituted in all these mutants by eliciting a replication fork stress with hydroxyurea. Cells expressing the Clb2(ME) mutant, that cannot bind Swe1, behaved like clb2Delta cells, and failed to accumulate Swe1 in the absence of Cdh1 or the presence of Cdc5(T29A). This suggests that for Swe1 to accumulate it must interact with Clb2. We further show that in the absence of Clb2, Hsl1 is no longer essential for Swe1 degradation. We hypothesize that Clb2-Cdk1 protects Swe1 from premature degradation until its Hsl1 mediated de-protection, which enables its Cdc5 mediated degradation. Swe1 levels are thus regulated by monitoring the levels of three major mitotic regulators.
机译：Swe1 / Wee1通过抑制Clb2-Cdk1调节有丝分裂进入，其积累涉及压力诱导G（2）逮捕。 APC / C（Cdh1）基板Cdc5，Clb2和Hsl1调节Swe1降解。我们观察到clb2Deltacdh1Delta双突变酿酒酵母不表达Swe1的任何可检测水平，大概是由于其组成性降解。 Cdh1失活的这种作用归因于Cdc5和Hsl1的稳定，因为clb2Delta细胞中不可降解的Cdc5（T29A）的表达阻止了Swe1的积累。令人惊讶的是，即使在野生型Clb2细胞中，不可降解的Hsl1（mdb / mkb）的表达也阻止了Swe1的积累。有趣的是，在所有这些突变体中，Swe1积累都可以通过用羟基脲引发复制叉应力来重建。表达不能结合Swe1的Clb2（ME）突变体的细胞的行为类似于clb2Delta细胞，并且在没有Cdh1或Cdc5（T29A）的情况下无法积累Swe1。这表明要使Swe1积累起来，它必须与Clb2相互作用。我们进一步表明，在没有Clb2的情况下，Hsl1不再是Swe1降解所必需的。我们假设，Clb2-Cdk1保护Swe1免受过早降解，直到它的Hsl1介导的去保护，从而使其Cdc5介导的降解成为可能。因此，通过监测三个主要的有丝分裂调节剂的水平来调节Swe1的水平。

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