Discrete roles of the Spc1 kinase and the Atf1 transcription factor in the UV response of Schizosaccharomyces pombe
Discrete roles of the Spc1 kinase and the Atf1 transcription factor in the UV response of Schizosaccharomyces pombe
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DOI：
10.1128/mcb.17.6.3356
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发表时间：
1997-06-01
影响因子：
5.3
通讯作者：
Russell, P
中科院分区：
文献类型：
--
作者：
Degols, G;Russell, P
哺乳动物细胞暴露于UV照射或烷化剂导致c-Jun N-末端激酶和p38应激活化蛋白激酶级联的激活，c-Jun和ATF-2 bZIP转录因子的磷酸化，并最终选择性诱导基因表达。这种紫外线反应被认为对细胞存活至关重要，尽管缺乏确凿的证据。sere，我们解决这个问题，通过调查一个同源的紫外线响应途径在裂殖酵母粟酒裂殖酵母。在裂殖酵母细胞中，紫外线照射诱导Spc 1应激激活蛋白激酶的激活，进而磷酸化Atf 1 bZIP转录因子，spc 1突变体对紫外线的杀伤高度敏感，其水平相当于一些检查点rad突变体。鉴于检查点rad突变体不能阻止分裂以响应DNA损伤，spc 1突变体在UV暴露后恢复细胞分裂方面存在缺陷，ctt 1（+）的基础和UV诱导转录水平在spc 1突变体中极低，ctt 1（+）编码过氧化氢酶，其被认为对对抗UV引起的氧化应激很重要。Atf 1是紫外线诱导ctt 1（+）转录所必需的，但atf 1突变体对紫外线的杀伤并不敏感。这一令人惊讶的发现可以通过观察到ctt 1（+）的基础表达在atf 1单突变体和spc 1 atf 1双突变体细胞中不受影响来解释，表明未磷酸化的Atf 1抑制了spc 1细胞中ctt 1（+）的表达。在bet中，spc 1 atf 1双突变体细胞的UV敏感性水平介于野生型和spc 1突变体细胞之间。这些研究结果表明：(i)紫外线反应机制的关键特性在哺乳动物和S。粟酒(ii)Spc 1激酶的激活大大提高了紫外线照射细胞的存活率。(iii)通过激活Atn诱导基因表达可能不是应激激活激酶在UV响应中发挥作用的最重要机制。
Exposure of mammalian cells to UV irradiation or alkylating agents leads to the activation of the c-Jun N-terminal kinase and p38 stress-activated protein kinase cascades, phosphorylation of c-Jun and ATF-2 bZIP transcription factors, and finally to selective induction of gene expression. This UV response is believed to be crucially important for cell survival, although conclusive evidence is lacking. sere, we address this issue by investigating a homologous UV response pathway in the fission yeast Schizosaccharomyces pombe. In fission yeast cells, UV irradiation induces activation of Spc1 stress-activated protein kinase, which in turn phosphorylates the Atf1 bZIP transcription factor, spc1 mutants are hypersensitive to killing by UV at a level equivalent to some checkpoint rad mutants. Whereas checkpoint rad mutants fail to arrest division in response to DNA damage, spc1 mutants are defective at resuming cell division after UV exposure, Levels of basal and UV-induced transcription of ctt1(+), which encodes a catalase believed important for combating oxidative stress caused by UV, are extremely low in spc1 mutants. Atf1 is required for W-induced transcription of ctt1(+), but atf1 mutants are not hypersensitive to killing by UV, This surprising finding is explained by the observation that ctt1(+) basal expression is unaffected in atf1 single mutant and spc1 atf1 double mutant cells, suggesting that unphosphorylated Atf1 represses ctt1(+) expression in spc1 cells. In bet, the level of UV sensitivity of spc1 atf1 double mutant cells is intermediate between those of the wild type and spc1 mutants. These findings suggest the following. (i) Key properties of UV response mechanisms are remarkably similar in mammals and S. pombe. (ii) Activation of Spc1 kinase greatly enhances survival of UV-irradiated cells. (iii) Induction of gene expression by activation of Atn may not, be the most important mechanism by which stress-activated kinases function in the UV response.