Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans.

dc.contributor.author

Lee, Kyung-Tae

dc.contributor.author

So, Yee-Seul

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Yang, Dong-Hoon

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Jung, Kwang-Woo

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Choi, Jaeyoung

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Lee, Dong-Gi

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Kwon, Hyojeong

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Jang, Juyeong

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Wang, Li Li

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Cha, Soohyun

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Meyers, Gena Lee

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Jeong, Eunji

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Jin, Jae-Hyung

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Lee, Yeonseon

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Hong, Joohyeon

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Bang, Soohyun

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Ji, Je-Hyun

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Park, Goun

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Byun, Hyo-Jeong

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Park, Sung Woo

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Park, Young-Min

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Adedoyin, Gloria

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Kim, Taeyup

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Averette, Anna F

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Choi, Jong-Soon

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Heitman, Joseph

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Cheong, Eunji

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Lee, Yong-Hwan

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Bahn, Yong-Sun

dc.coverage.spatial

England

dc.date.accessioned

2016-12-01T14:40:38Z

dc.date.issued

2016-09-28

dc.description.abstract

Cryptococcus neoformans is the leading cause of death by fungal meningoencephalitis; however, treatment options remain limited. Here we report the construction of 264 signature-tagged gene-deletion strains for 129 putative kinases, and examine their phenotypic traits under 30 distinct in vitro growth conditions and in two different hosts (insect larvae and mice). Clustering analysis of in vitro phenotypic traits indicates that several of these kinases have roles in known signalling pathways, and identifies hitherto uncharacterized signalling cascades. Virulence assays in the insect and mouse models provide evidence of pathogenicity-related roles for 63 kinases involved in the following biological categories: growth and cell cycle, nutrient metabolism, stress response and adaptation, cell signalling, cell polarity and morphology, vacuole trafficking, transfer RNA (tRNA) modification and other functions. Our study provides insights into the pathobiological signalling circuitry of C. neoformans and identifies potential anticryptococcal or antifungal drug targets.

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/27677328

dc.identifier

ncomms12766

dc.identifier.eissn

2041-1723

dc.identifier.uri

https://hdl.handle.net/10161/13057

dc.language

eng

dc.publisher

Springer Science and Business Media LLC

dc.relation.ispartof

Nat Commun

dc.relation.isversionof

10.1038/ncomms12766

dc.title

Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans.

dc.type

Journal article

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/27677328

pubs.begin-page

12766

pubs.organisational-group

Basic Science Departments

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Clinical Science Departments

pubs.organisational-group

Duke

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Duke Cancer Institute

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Institutes and Centers

pubs.organisational-group

Medicine

pubs.organisational-group

Medicine, Infectious Diseases

pubs.organisational-group

Molecular Genetics and Microbiology

pubs.organisational-group

Pharmacology & Cancer Biology

pubs.organisational-group

School of Medicine

pubs.publication-status

Published online

pubs.volume

7

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