Department of Pathogen Biology, School of Medicine, Nantong University, No.19 Qixiu Road, Nantong City, Jiangsu Province, Nantong 226001, China.
FEMS Yeast Res. 2019 Dec 1;19(8). doi: 10.1093/femsyr/foz075.
In the pathogenic fungus Candida albicans, phosphoregulation of the checkpoint kinase Rad53 plays a crucial role in the filamentous growth response to genotoxic stresses. The protein phosphatase 4 (PP4) complex, containing Pph3 and either Psy2 or Psy4, is proved to play a critical role in Rad53 dephosphorylation. In previous studies, we characterized CaPtc2 (the ortholog of both Ptc2 and Ptc3 in Saccharomyces cerevisiae) as a potential DNA-damage-related protein phosphatase. In this study, we checked the genetic interaction of PTC2 with the PP4 complex in the DNA damage response pathway. The results suggest that Ptc2 shows a negative genetic interaction with Pph3, but positive genetic interaction with either Psy2 or Psy4 in response to genotoxic stress. Deletion of PTC2 alone resulted in no significant change in cell virulence, but double deletion of PTC2 PPH3 significantly decreased virulence, while double deletions of either PTC2 PSY2 or PTC2 PSY4 caused virulence levels similar to that shown by PSY2 or PSY4 single-gene deletion cells. Taken together, we propose that Ptc2 in C. albicans plays a compensatory role for Pph3 but is dependent on Psy2 and Psy4 in regulation of DNA damage and cell virulence.
在致病性真菌白色念珠菌中，检查点激酶 Rad53 的磷酸化调节在丝状生长对遗传毒性应激的反应中起着至关重要的作用。蛋白磷酸酶 4（PP4）复合物，包含 Pph3 和 Psy2 或 Psy4 中的任一个，被证明在 Rad53 去磷酸化中起关键作用。在之前的研究中，我们将 CaPtc2（酿酒酵母中 Ptc2 和 Ptc3 的同源物）鉴定为一种潜在的与 DNA 损伤相关的蛋白磷酸酶。在这项研究中，我们检查了 PTC2 与 PP4 复合物在 DNA 损伤反应途径中的遗传相互作用。结果表明，Ptc2 与 Pph3 表现出负遗传相互作用，但与 Psy2 或 Psy4 表现出正遗传相互作用，以响应遗传毒性应激。单独缺失 PTC2 不会导致细胞毒力显著变化，但 PTC2PPH3 双缺失显著降低毒力，而 PTC2PSY2 或 PTC2PSY4 的双缺失导致的毒力水平与 Psy2 或 Psy4 单基因缺失细胞相似。综上所述，我们提出白色念珠菌中的 Ptc2 对 Pph3 起补偿作用，但在调节 DNA 损伤和细胞毒力方面依赖于 Psy2 和 Psy4。
