Peroxide sensors for the fission yeast stress-activated mitogen-activated protein kinase pathway
Peroxide sensors for the fission yeast stress-activated mitogen-activated protein kinase pathway
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DOI：
10.1091/mbc.12.2.407
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发表时间：
2001-02-01
影响因子：
3.3
通讯作者：
Millar, JBA
中科院分区：
文献类型：
--
作者：
Buck, V;Quinn, J;Millar, JBA
裂殖酵母应力激活Sty 1 p/Spc 1 p丝裂原激活蛋白（MAP）激酶通过Atf 1 p和Pap 1 p转录因子调节基因表达，Atf 1 p和Pap 1 p分别是人ATF 2和c-jun的同源物。Mcs 4p是一种反应调节蛋白，通过结合Wak 1 p/Wis 4p MAP激酶激酶激酶而作用于Sty 1 p的上游。我们发现磷酸化。在保守的天冬氨酸残基上的Mcs 4p是激活Sty 1 p所必需的，只有在响应过氧化物胁迫。Mcs 4p在由两个含有PAS/PAC结构域的组氨酸激酶Mak 2 p和Mak 3 p启动的保守磷酸化中继系统中起作用。在Mak 2 p或Mak 3 p的情况下，Sty 1 p不能磷酸化Atf 1 p转录因子或诱导Atf 1 p依赖性基因表达。因此，缺乏Mak 2 p和Mak 3 p的细胞在缺乏Prr 1 p的情况下对过氧化物攻击敏感，Prr 1 p是一种与Pap 1 p相关的独特反应调节蛋白。Mak 1 p组氨酸激酶也含有PAS/PAC重复序列，不调节Sty 1 p或Atf 1 p，但部分需要Pap 1 p和Prr 1 p依赖性转录。我们的结论是，在裂变酵母的转录响应自由基攻击发起至少两个不同的磷酸中继途径。
The Schizosaccharomyces pombe stress-activated Sty1p/Spc1p mitogen-activated protein (MAP) kinase regulates gene expression through the Atf1p and Pap1p transcription factors, homologs of human ATF2 and c-jun, respectively. Mcs4p, a response regulator protein, acts upstream of Sty1p by binding the Wak1p/Wis4p MAP kinase kinase kinase. We show that phosphorylation. of Mcs4p on a conserved aspartic acid residue is required for activation of Sty1p only in response to peroxide stress. Mcs4p acts in a conserved phospho-relay system initiated by two PAS/PAC domain-containing histidine kinases, Mak2p and Mak3p. In the absence of Mak2p or Mak3p, Sty1p fails to phosphorylate the Atf1p transcription factor or induce Atf1p-dependent gene expression. As a consequence, cells lacking Mak2p and Mak3p are sensitive to peroxide attack in the absence of Prr1p, a distinct response regulator protein that functions in association with Pap1p. The Mak1p histidine kinase, which also contains PAS/PAC repeats, does not regulate Sty1p or Atf1p but is partially required for Pap1p- and Prr1p-dependent transcription. We conclude that the transcriptional response to free radical attack is initiated by at least two distinct phospho-relay pathways in fission yeast.