PXD012983-1

PXD012983 is an original dataset announced via ProteomeXchange.

Title	Cryptococcus neoformans TOR1 phosphoproteomics
Description	The target of rapamycin (TOR) pathway is an evolutionarily conserved signal transduction system that is activated by varying nutrient and environmental signals and governs a plethora of eukaryotic biological processes. Nevertheless, its role in the human fungal pathogen Cryptococcus neoformans remains elusive. In this study, we investigated the TOR pathway by functionally characterizing two Tor-like kinases, Tor1 and Tlk1, in C. neoformans. We successfully deleted TLK1, but not TOR1. TLK1 deletion did not result in any evident in vitro phenotypes, except for a minor role in diamide and polyene resistance, suggesting that Tlk1 is mainly dispensable for the growth of C. neoformans. We further demonstrated that Tor1, but not Tlk1, is essential and the target of rapamycin by constructing and analyzing conditionally regulated strains and sporulation analysis of heterozygous mutants in the diploid strain background. To analyze the functions of Tor1 in more detail, we constructed constitutive TOR1 overexpression strains. Tor1 negatively regulated thermotolerance and the DNA damage response, which are two important virulence factors of C. neoformans. We also found that TOR1 overexpression reduced Mpk1 phosphorylation, which is required for cell wall integrity and thermoresistance, and Rad53 phosphorylation, which governs the DNA damage response pathway. Tor1 is localized to the cytoplasm but enriched in the vacuole membrane. Phosphoproteomics and transcriptomics revealed that Tor1 regulates a variety of biological processes, including metabolic processes, cytoskeleton organization, ribosome biogenesis, autophagy, and stress response. Finally, screening rapamycin-sensitive and -resistant kinase and transcription factor mutants revealed that the TOR pathway may crosstalk with a number of signaling pathways, including the Hog1 pathway. In conclusion, our study demonstrates that a single Tor1 kinase plays a variety of roles in the fungal meningitis pathogen C. neoformans.
HostingRepository	PRIDE
AnnounceDate	2019-08-19
AnnouncementXML	Submission_2019-08-19_00:03:39.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD012983
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Dong-Gi Lee
SpeciesList	scientific name: Cryptococcus neoformans var. grubii H99S; NCBI TaxID: 1432137;
ModificationList	Phospho; Oxidation; Acetyl; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-05 08:40:05	ID requested
⏵ 1	2019-08-19 00:03:41	announced

So YS, Lee DG, Idnurm A, Ianiri G, Bahn YS, . Genetics, 212(4):1241-1258(2019) [pubmed]

curator keyword: Biological

submitter keyword: Cryptococcus, CnTOR1, phosphoproteomics

Yong-Sun Bahn
contact affiliation	Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
contact email	ysbahn@yonsei.ac.kr
lab head
Dong-Gi Lee
contact affiliation	Yonsei University
contact email	leedonggi2@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012983
     1. Label: PRIDE project
     2. Name: Cryptococcus neoformans TOR1 phosphoproteomics