Negative regulation of calcineurin signaling by Hrr25p, a yeast homolog of casein kinase I
Negative regulation of calcineurin signaling by Hrr25p, a yeast homolog of casein kinase I
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DOI：
10.1101/gad.1140603
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发表时间：
2003-11-01
影响因子：
10.5
通讯作者：
Cyert, MS
中科院分区：
文献类型：
--
作者：
Kafadar, KA;Zhu, H;Cyert, MS
钙调神经磷酸酶是一种由钙调蛋白调节的蛋白磷酸酶，是酿酒酵母对各种环境胁迫反应所必需的。钙调神经磷酸酶通过去磷酸化和激活锌指转录因子Crz 1 p/Tcn 1 p促进细胞在应激过程中的存活。使用高通量测定，我们筛选了119酵母激酶的能力，在体外磷酸化Crz 1 p和确定的酪蛋白激酶I同源Hrr 25 p。在这里，我们表明，Hrr 25 p负调控Crz 1 p活性和核定位在体内。在体外和体内，Hrr 25 p结合并磷酸化Crz 1 p。Hrr 25 p的过表达降低Crz 1 p依赖的转录，并拮抗其Ca 2+诱导的核积累。在Hrr 25 p的情况下，激活Crz 1 p的Ca 2 +/钙调神经磷酸酶是加强。这些发现代表了Crz 1 p的负调节剂的首次鉴定，并建立了Hrr 25 p在拮抗钙调磷酸酶信号传导中的新生理作用。
Calcineurin is a Ca2+/calmodulin-regulated protein phosphatase required for Saccharomyces cerevisiae to respond to a variety of environmental stresses. Calcineurin promotes cell survival during stress by dephosphorylating and activating the Zn-finger transcription factor Crz1p/Tcn1p. Using a high-throughput assay, we screened 119 yeast kinases for their ability to phosphorylate Crz1p in vitro and identified the casein kinase I homolog Hrr25p. Here we show that Hrr25p negatively regulates Crz1p activity and nuclear localization in vivo. Hrr25p binds to and phosphorylates Crz1p in vitro and in vivo. Overexpression of Hrr25p decreases Crz1p-dependent transcription and antagonizes its Ca2+-induced nuclear accumulation. In the absence of Hrr25p, activation of Crz1p by Ca2+/calcineurin is potentiated. These findings represent the first identification of a negative regulator for Crz1p, and establish a novel physiological role for Hrr25p in antagonizing calcineurin signaling.