Regulation of Schizosaccharomyces pombe Atf 1 protein levels by Sty1-mediated phosphorylation and heterodimerization with Pcr1
Regulation of Schizosaccharomyces pombe Atf 1 protein levels by Sty1-mediated phosphorylation and heterodimerization with Pcr1
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DOI：
10.1074/jbc.m608526200
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发表时间：
2007-02-23
影响因子：
4.8
通讯作者：
Jones, Nic
中科院分区：
文献类型：
--
作者：
Lawrence, Clare L.;Maekarwa, Hiromi;Jones, Nic
Atf 1转录因子在粟酒裂殖酵母细胞响应各种胁迫条件的能力中起着至关重要的作用。它以应激依赖的方式调节许多基因的表达，其功能依赖于应激激活的MAPK，Sty 1/Spc 1。此外，Atf 1直接被Sty 1磷酸化。在这里，我们研究了这种磷酸化的作用。Atf 1蛋白积累的压力，这种积累是失去了一个菌株缺陷的Sty 1信号通路。此外，不能再被磷酸化的突变体Atf 1 I蛋白的积累丧失。Atf 1半衰期的测量表明，Atf 1稳定性的变化是导致这种蓄积的原因。Atf 1的稳定性也受到其异二聚体伴侣Pcr 1的调节。同样，Pcr 1水平受Atf 1调节。因此，存在多种途径，以确保Atf 1水平得到适当的调节。Atf 1的磷酸化对于细胞对H2 O2应激产生强有力的反应是重要的，因为Atf 1磷酸化突变体显示出对这种应激的敏感性，并且基因表达的诱导低于在野生型细胞中观察到的。然而，令人惊讶的是，Atfl I磷酸化的丧失并不导致Atfl靶基因的应激激活表达的完全丧失。因此，Atf 1磷酸化突变体不显示与atf 1缺失突变体相同的总体应力敏感性。总之，这些数据表明，Sty 1的Atf 1磷酸化是不需要激活Atf 1本身，而是调节其稳定性。
The Atf1 transcription factor plays a vital role in the ability of Schizosaccharomyces pombe cells to respond to various stress conditions. It regulates the expression of many genes in a stress-dependent manner, and its function is dependent upon the stress-activated MAPK, Sty1/Spc1. Moreover, Atf1 is directly phosphorylated by Sty1. Here we have investigated the role of such phosphorylation. Atf1 protein accumulates following stress, and this accumulation is lost in a strain defective in the Sty1 signaling pathway. In addition, accumulation of a mutant Atf1 I protein that can no longer be phosphorylated is lost. Measurement of the half-life of Atf1 demonstrates that changes in Atf1 stability are responsible for this accumulation. Atf1 stability is also regulated by its heterodimeric partner, Pcr1. Similarly, Pcr1 levels are regulated by Atf1. Thus multiple pathways exist that ensure that Atf1 levels are appropriately regulated. Phosphorylation of Atf1 is important for cells to mount a robust response to H2O2 stress, because the Atf1 phospho-mutant displays sensitivity to this stress, and induction of gene expression is lower than that observed in wild-type cells. Surprisingly, however, loss of Atf1 I phosphorylation does not lead to the complete loss of stress-activated expression of Atf1 target genes. Accordingly, the Atf1 phospho-mutant does not display the same overall stress sensitivities as the atf1 deletion mutant. Taken together, these data suggest that Sty1 phosphorylation of Atf1 is not required for activation of Atf1 per se but rather for modulating its stability.