Regulation of G0 entry by the Pho80-Pho85 cyclin-CDK complex
Regulation of G0 entry by the Pho80-Pho85 cyclin-CDK complex
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DOI：
10.1038/sj.emboj.7600889
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发表时间：
2005-12-21
期刊：
影响因子：
11.4
通讯作者：
De Virgilio, C
中科院分区：
文献类型：
--
作者：
Wanke, V;Pedruzzi, I;De Virgilio, C
真核细胞增殖受生长因子和必需营养素的控制。在它们不存在的情况下，细胞可以进入静止状态（G（0））。在酿酒酵母中，保守的蛋白激酶A（PKA）和雷帕霉素敏感性TOR（TORC 1）途径主要通过抑制PAS激酶Rim 15功能来拮抗G（0）进入，以响应碳和/或氮的可用性。在这里，我们表明，磷酸盐敏感的Pho 80-Pho 85细胞周期蛋白依赖性激酶（CDK）复合物也参与Rim 15抑制通过直接磷酸化，从而有效地隔离Rim 15在细胞质中通过其与14-3-3蛋白。Pho 80-Pho 85或TORC 1的失活导致Rim 15中14-3-3-结合位点的去磷酸化，从而使Rim 15能够进入核内并诱导Rim 15控制的G（0）程序。重要的是，我们还表明，Pho 80-Pho 85和TORC 1收敛于Rim 15中的单个氨基酸。因此，Rim 15通过其整合PKA、TORC 1和Pho 80-Pho 85通路信号的能力在G（0）进入中起关键作用。
Eukaryotic cell proliferation is controlled by growth factors and essential nutrients. In their absence, cells may enter into a quiescent state (G(0)). In Saccharomyces cerevisiae, the conserved protein kinase A (PKA) and rapamycin-sensitive TOR (TORC1) pathways antagonize G(0) entry in response to carbon and/or nitrogen availability primarily by inhibiting the PAS kinase Rim15 function. Here, we show that the phosphate-sensing Pho80-Pho85 cyclin-cyclin-dependent kinase (CDK) complex also participates in Rim15 inhibition through direct phosphorylation, thereby effectively sequestering Rim15 in the cytoplasm via its association with 14-3-3 proteins. Inactivation of either Pho80-Pho85 or TORC1 causes dephosphorylation of the 14-3-3-binding site in Rim15, thus enabling nuclear import of Rim15 and induction of the Rim15-controlled G(0) program. Importantly, we also show that Pho80-Pho85 and TORC1 converge on a single amino acid in Rim15. Thus, Rim15 plays a key role in G(0) entry through its ability to integrate signaling from the PKA, TORC1, and Pho80-Pho85 pathways.