title: CaTip41 regulates protein phosphatase 2A activity, CaRad53 deactivation and the recovery of DNA damage-induced filamentation to yeast form in Candida albicans.
abstract: Phosphorylation and dephosphorylation of the checkpoint kinase CaRad53 is crucial for fungal cells in response to genotoxic stresses. The protein phosphatase 2A (PP2A) CaPph3/CaPsy2 phosphatase complex is involved in CaRad53 dephosphorylation in Candida albicans. In view of the role of ScTip41/ScTap42 in regulating PP2A phosphatases in Saccharomyces cerevisiae, we have explored the function of CaTip41 in C. albicans. Here, we show that CaTIP41 is a functional ortholog of ScTIP41 in the sensitivity of S. cerevisiae cells to rapamycin. Deletion of CaTIP41 causes C. albicans cells to be sensitive to DNA damaging agents, methylmethane sulfonate (MMS) and cisplatin, and resistant to both rapamycin and caffeine. Accordingly, expression of CaTip41 increases in response to MMS and cisplatin. In addition, C. albicans cells lacking CaTIP41 show a delay in the recovery from MMS-induced filamentation to yeast form, decreased PP2A activity and a defect in deactivation of CaRad53 during recovery from DNA damage. Through yeast two-hybrid assay we show that CaTip41 interacts with either CaPph3, CaPsy2 or CaTap42. Therefore, CaTip41 plays regulatory roles in both the CaRad53 deactivation during recovery from DNA damage and the target of rapamycin signaling pathway.
authors: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong 226001, China.
authors: Jinrong
authors: J
authors: Feng
authors: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong 226001, China.
authors: Yinong
authors: Y
authors: Duan
authors: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong 226001, China.
authors: Wei
authors: W
authors: Sun
authors: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong 226001, China.
authors: Yongwei
authors: Y
authors: Qin
authors: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong 226001, China.
authors: Zhong
authors: Z
authors: Zhuang
authors: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong 226001, China.
authors: Dandan
authors: D
authors: Zhu
authors: Department of Pathogen Biology, School of Medicine, Nantong University, Nantong 226001, China.
authors: Xiaolei
authors: X
authors: Sun
authors: The National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi 214122, China linghuojiang@hotmail.com.
authors: Linghuo
authors: L
authors: Jiang
mesh_terms: D002110:Caffeine / Q000378:metabolism; D002176:Candida albicans / Q000166:cytology* / Q000187:drug effects / Q000235:genetics*; D064447:Checkpoint Kinase 2 / Q000378:metabolism*; D002945:Cisplatin / Q000633:toxicity; D004249:DNA Damage; D004260:DNA Repair; D015966:Gene Expression Regulation, Fungal; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008741:Methyl Methanesulfonate / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D020123:Sirolimus / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009153:Mutagens; D002110:Caffeine; D008741:Methyl Methanesulfonate; D064447:Checkpoint Kinase 2; D054648:Protein Phosphatase 2; D002945:Cisplatin; D020123:Sirolimus
keywords: DNA damage; MMS; PP2A; RAD53; rapamycin