The yeast Ess1 prolyl isomerase controls Swi6 and Whi5 nuclear localization.
The yeast Ess1 prolyl isomerase controls Swi6 and Whi5 nuclear localization.
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DOI：
10.1534/g3.113.008763
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发表时间：
2014-03-20
期刊：
影响因子：
--
通讯作者：
Hanes SD
中科院分区：
文献类型：
--
作者：
Atencio D;Barnes C;Duncan TM;Willis IM;Hanes SD
来自酿酒酵母（Saccharomycescerevisiae）及其人类直系同源物Pin 1的PIN 1脯氨酰异构酶通过调节RNA聚合酶II在转录中起关键作用。在人类细胞中，Pin 1还调节多种信号蛋白，Pin 1的错误表达与几种人类疾病有关。为了深入了解PIN 1/Pin 1的功能，我们进行了合成基因阵列筛选，以确定酵母中PIN 1的新靶点。我们确定了转录，应激和细胞周期途径中的潜在靶点。我们专注于细胞周期调节Swi 6和Whi 5，这两个都显示出高度调节核质穿梭在细胞周期。令人惊讶的是，BMP 1并不控制它们的转录，而是它们的核定位所必需的。在体内，RIP 1与Swi 6和Whi 5相关，在体外，RIP 1直接与对应于它们的核定位序列的肽结合。只有当Swi 6和Whi 5肽在Ser-Pro基序（细胞周期蛋白依赖性激酶的靶位点）磷酸化时，才能与BMP 1结合。在这些结果的基础上，我们提出了一个模型，在该模型中，EST 1诱导的构象开关（顺反异构化）在磷酸丝氨酸-Pro网站内的核靶向序列Swi 6和Whi 5。这种开关将促进核进入和/或保留在后期M和G1期，并可能通过刺激这些网站的Cdc 14磷酸酶的去磷酸化。这是第一个确定酵母中除RNA聚合酶II以外的靶点的研究。
The Ess1 prolyl isomerase from Saccharomyces cerevisiae and its human ortholog, Pin1, play critical roles in transcription by regulating RNA polymerase II. In human cells, Pin1 also regulates a variety of signaling proteins, and Pin1 misexpression is linked to several human diseases. To gain insight into Ess1/Pin1 function, we carried out a synthetic genetic array screen to identify novel targets of Ess1 in yeast. We identified potential targets of Ess1 in transcription, stress, and cell-cycle pathways. We focused on the cell-cycle regulators Swi6 and Whi5, both of which show highly regulated nucleocytoplasmic shuttling during the cell cycle. Surprisingly, Ess1 did not control their transcription but instead was necessary for their nuclear localization. Ess1 associated with Swi6 and Whi5 in vivo and bound directly to peptides corresponding to their nuclear localization sequences in vitro. Binding by Ess1 was significant only if the Swi6 and Whi5 peptides were phosphorylated at Ser-Pro motifs, the target sites of cyclin-dependent kinases. On the basis of these results, we propose a model in which Ess1 induces a conformational switch (cis-trans isomerization) at phospho-Ser-Pro sites within the nuclear targeting sequences of Swi6 and Whi5. This switch would promote nuclear entry and/or retention during late M and G1 phases and might work by stimulating dephosphorylation at these sites by the Cdc14 phosphatase. This is the first study to identify targets of Ess1 in yeast other than RNA polymerase II.
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DOI：
10.1083/jcb.138.3.629
发表时间：
1997-08-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Carminati JL;Stearns T
通讯作者：
Stearns T
影响因子：
6
作者：
Bao, L;Kimzey, A;Wang, DG
通讯作者：
Wang, DG
影响因子：
4.8
作者：
Hani, J;Schelbert, B;Rahfeld, JU
通讯作者：
Rahfeld, JU
影响因子：
4.5
作者：
Gilbert, W;Siebel, CW;Guthrie, C
通讯作者：
Guthrie, C
DOI：
10.1073/pnas.0900604106
发表时间：
2009-06-23
影响因子：
11.1
作者：
Kosugi, Shunichi;Hasebe, Masako;Yanagawa, Hiroshi
通讯作者：
Yanagawa, Hiroshi