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Although extensive studies have been conducted on signal transduction pathways important for fungal sexual reproduction and virulence, how fungal virulence is regulated during infection is still not understood. In this study, we identified the F-box protein Fbp1, which contains a putative F-box domain and 12 leucine-rich repeats (LRR). Although<jats:named-content content-type=\"genus-species\">fbp1<\/jats:named-content>mutants showed normal growth and produced normal major virulence factors, such as melanin and capsule, Fbp1 was found to be essential for fungal virulence, as<jats:named-content content-type=\"genus-species\">fbp1<\/jats:named-content>mutants were avirulent in a murine systemic-infection model. Fbp1 is also important for fungal sexual reproduction. Basidiospore production was blocked in bilateral mating between<jats:named-content content-type=\"genus-species\">fbp1<\/jats:named-content>mutants, even though normal dikaryotic hyphae were observed during mating.<jats:italic>In vitro<\/jats:italic>assays of stress responses revealed that<jats:named-content content-type=\"genus-species\">fbp1<\/jats:named-content>mutants are hypersensitive to SDS, but not calcofluor white (CFW) or Congo red, indicating that Fbp1 may regulate cell membrane integrity. Fbp1 physically interacts with Skp1 homologues in both<jats:named-content content-type=\"genus-species\">Saccharomyces cerevisiae<\/jats:named-content>and<jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>via its F-box domain, suggesting it may function as part of an SCF (Skp1, Cullins, F-box proteins) E3 ligase. Overall, our study revealed that the F-box protein Fbp1 is essential for fungal sporulation and virulence in<jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>, which likely represents a conserved novel virulence control mechanism that involves the SCF E3 ubiquitin ligase-mediated proteolysis pathway.<\/jats:p>","DOI":"10.1128\/ec.00004-11","type":"journal-article","created":{"date-parts":[[2011,4,9]],"date-time":"2011-04-09T03:14:10Z","timestamp":1302318850000},"page":"791-802","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":61,"title":["The F-Box Protein Fbp1 Regulates Sexual Reproduction and Virulence in Cryptococcus neoformans"],"prefix":"10.1128","volume":"10","author":[{"given":"Tong-Bao","family":"Liu","sequence":"first","affiliation":[{"name":"Public Health Research Institute, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School, Newark, New Jersey 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yina","family":"Wang","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School, Newark, New Jersey 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabriya","family":"Stukes","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Chen","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School, Newark, New Jersey 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Casadevall","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyang","family":"Xue","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School, Newark, New Jersey 07103"},{"name":"Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey (UMDNJ)-New Jersey Medical School, Newark, New Jersey 07103"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.23.3206"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e05-01-0079"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04-11-0987"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1578"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06955.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00399-06"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1639"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(01)02412-7"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/155.3.1033"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2006.03.004"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/9781555818241"},{"key":"e_1_3_3_13_2","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1111\/j.1365-2958.2008.06310.x","article-title":"Role and mechanism of phosphatidylinositol-specific phospholipase C in survival and virulence of Cryptococcus neoformans","volume":"69","author":"Chayakulkeeree M.","year":"2008","unstructured":"ChayakulkeereeM.. 2008. 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