The Pbs2 MAP kinase kinase is essential for the oxidative-stress response in the fungal pathogen Candida albicans
The Pbs2 MAP kinase kinase is essential for the oxidative-stress response in the fungal pathogen Candida albicans
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DOI：
10.1099/mic.0.27723-0
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发表时间：
2005-04-01
期刊：
影响因子：
2.8
通讯作者：
Pla, J
中科院分区：
文献类型：
--
作者：
Arana, DM;Nombela, C;Pla, J
人类真菌病原体白色念珠菌对压力的反应是通过Hog1 MAP激酶的磷酸化。PBS2被克隆并被证明编码参与这种激活的MAP激酶，这是通过使用识别目标Hog1蛋白的活性形式的抗体进行免疫印迹分析确定的。对PBS2突变体的鉴定表明，它们对渗透和氧化应激都很敏感，有趣的是，它们表现出与hog1突变体不同的行为，在受到氧化挑战时比hog1菌株更快地丧失活力。Hog1和PBS2也被证明参与了对氧化应激的适应机制，与野生型相比，PBS2和Hog1突变体对氧化剂的敏感性增强，当细胞预先暴露在低浓度、亚致死浓度的过氧化氢中时，以及在适应过程中依赖于PBS2的Hog1 MAP激酶活性降低。对嵌合的Hog1-绿色荧光蛋白融合的研究表明，该蛋白定位于整个细胞(排除在液泡之外)，但对盐胁迫的反应集中在细胞核，这一过程依赖于PBS2蛋白。Hog 1和PBS2也在控制其他MAP激酶Mkc1和CEK1的磷酸化状态方面发挥作用，它们分别参与细胞壁完整性和侵袭性生长。此外，已证明PBS2在该真菌的细胞壁生物发生中起作用，因为它的缺失导致细胞对某些干扰细胞壁的化合物的敏感性发生改变。
The human fungal pathogen Candida albicans responds to stress by phosphorylation of the Hog1 MAP kinase. PBS2 was cloned and shown to encode the MAP kinase kinase that is involved in this activation, as determined by immunoblot analyses using antibodies that recognize the active form of the target Hog1 protein. Characterization of pbs2 mutants revealed that they were sensitive to both osmotic and oxidative stress and that they, interestingly, displayed differential behaviour from that of hog1 mutants, losing viability when exposed to an oxidative challenge more rapidly than the hog1 strain. Hog1 and Pbs2 were also shown to be involved in the mechanism of adaptation to oxidative stress, as evidenced by the enhanced susceptibility to oxidants of pbs2 and hogl mutants, compared with the wild-type strain, when cells were previously exposed to a low, sub-lethal concentration of hydrogen peroxide and by the PBS2-dependent diminished activation of Hog1 MAP kinase in the adaptive process. Studies with a chimaeric Hog1-green fluorescent protein fusion revealed that this protein was localized throughout the cell (being excluded from the vacuole), but concentrated in the nucleus in response to NaCl stress, a process that was dependent on the Pbs2 protein. Both Hog 1 and Pbs2 also play a role in controlling the phosphorylation state of the other MAP kinases Mkc1 and Cek1, involved respectively in cell-wall integrity and invasive growth. Furthermore, it is demonstrated that PBS2 plays a role in cell-wall biogenesis in this fungal pathogen, as its deletion renders cells with an altered susceptibility to certain cell wall-interfering compounds.