Protein phosphatase PP4 is composed of one catalytic subunit and one or two regulatory subunits and conserved in eukaryotic cells. The catalytic subunit CaPph3 forms a complex with the regulatory subunit CaPsy2, which dephosphorylates activated CaRad53 during adaptation to and recovery from MMS-mediated DNA damage. We show here that the N-terminal Y33A mutation of CaPsy2 blocks the interaction between CaPph3 and CaRad53, the deactivation of CaRad53 and the morphologic switch in recovery from genotoxic stress. In Saccharomyces cerevisiae, the ScPph3-ScPsy2-ScPsy4 complex functions to dephosphorylate γH2A. In this study, we show that CaPsy4 is a functional homolog of ScPsy4 and not involved in the deactivation of CaRad53 or CaHta, the ortholog of H2A. However, deletion of CaPSY4 causes C. albicans cells a sensitivity to genotoxic reagents and a defect in DNA damage-induced filamentation. CaPsy4 interacts with both CaPph3 and CaPsy2, but the function of CaPsy4 is independent of CaPph3 and CaPsy2 in response to genotoxic stress. C. albicans cells lacking CaPPH3, CaPSY2 or CaPSY4, and C. albicans cells carrying the Y33A mutation of CaPSY2, show increased virulence to mice. Therefore, PP4 plays a negative role in regulating the DNA damage-induced filamentation and the virulence in C. albicans.

中文翻译：

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CaPsy2的N末端pY33XL基序对于蛋白质磷酸酶4在CaRad53失活，DNA损伤诱导的丝化和白色念珠菌的毒力中的功能至关重要。

蛋白磷酸酶PP4由一个催化亚基和一个或两个调节亚基组成，并在真核细胞中保守。催化亚基CaPph3与调节性亚基CaPsy2形成复合物，在适应MMS介导的DNA损伤并从中恢复时，它会磷酸化活化的CaRad53。我们在这里显示，CaPsy2的N末端Y33A突变可阻止CaPph3与CaRad53之间的相互作用，CaRad53的失活以及从遗传毒性胁迫中恢复的形态转换。在酿酒酵母中，ScPph3-ScPsy2-ScPsy4复合物的功能是使γH2A去磷酸化。在这项研究中，我们表明CaPsy4是ScPsy4的功能同源物，并且不参与Ca2 +的直系同源物CaRad53或CaHta的失活。但是，CaPSY4的缺失会导致C。白色念珠菌细胞对遗传毒性试剂敏感，并在DNA损伤诱导的丝化中存在缺陷。CaPsy4与CaPph3和CaPsy2都相互作用，但是CaPsy4的功能独立于CaPph3和CaPsy2，以应对遗传毒性胁迫。缺少CaPPH3，CaPSY2或CaPSY4的白色念珠菌细胞，以及带有CaPSY2的Y33A突变的白色念珠菌细胞，对小鼠的毒性增加。因此，PP4在调节白色念珠菌的DNA损伤诱导的丝化和毒力中起负作用。