{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:21:26Z","timestamp":1780406486351,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012269","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T00:00:00Z","timestamp":1718064000000}}],"reference-count":89,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T00:00:00Z","timestamp":1717027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["RO1AI150240"],"award-info":[{"award-number":["RO1AI150240"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI136511"],"award-info":[{"award-number":["R01AI136511"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI158417"],"award-info":[{"award-number":["R01AI158417"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21AI172206"],"award-info":[{"award-number":["R21AI172206"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P20GM113131"],"award-info":[{"award-number":["P20GM113131"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Toxoplasma gondii<\/jats:italic> is a foodborne pathogen that can cause severe and life-threatening infections in fetuses and immunocompromised patients. Felids are its only definitive hosts, and a wide range of animals, including humans, serve as intermediate hosts. When the transmissible bradyzoite stage is orally ingested by felids, they transform into merozoites that expand asexually, ultimately generating millions of gametes for the parasite sexual cycle. However, bradyzoites in intermediate hosts differentiate exclusively to disease-causing tachyzoites, which rapidly disseminate throughout the host. Though tachyzoites are well-studied, the molecular mechanisms governing transitioning between developmental stages are poorly understood. Each parasite stage can be distinguished by a characteristic transcriptional signature, with one signature being repressed during the other stages. Switching between stages require substantial changes in the proteome, which is achieved in part by ubiquitination. F-box proteins mediate protein poly-ubiquitination by recruiting substrates to SKP1, Cullin-1, F-Box protein E3 ubiquitin ligase (SCF-E3) complexes. We have identified an F-box protein named <jats:italic>Toxoplasma gondii<\/jats:italic> F-Box Protein L2 (TgFBXL2), which localizes to distinct perinucleolar sites. TgFBXL2 is stably engaged in an SCF-E3 complex that is surprisingly also associated with a COP9 signalosome complex that negatively regulates SCF-E3 function. At the cellular level, TgFBXL2-depleted parasites are severely defective in centrosome replication and daughter cell development. Most remarkable, RNAseq data show that TgFBXL2 conditional depletion induces the expression of stage-specific genes including a large cohort of genes necessary for sexual commitment. Together, these data suggest that TgFBXL2 is a latent guardian of stage specific gene expression in <jats:italic>Toxoplasma<\/jats:italic> and poised to remove conflicting proteins in response to an unknown trigger of development.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012269","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T17:44:58Z","timestamp":1717091098000},"page":"e1012269","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Toxoplasma gondii F-Box Protein L2 Functions as a Repressor of Stage Specific Gene Expression"],"prefix":"10.1371","volume":"20","author":[{"given":"Carlos 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Roch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"West","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7783-3818","authenticated-orcid":true,"given":"Ira J.","family":"Blader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,30]]},"reference":[{"issue":"12","key":"ppat.1012269.ref001","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.ijpara.2009.04.003","article-title":"Toxoplasmosis snapshots: global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis","volume":"39","author":"G Pappas","year":"2009","journal-title":"Int J 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A morphological analysis]","volume":"29","author":"E van der Zypen","year":"1967","journal-title":"Z Parasitenkd"},{"issue":"7","key":"ppat.1012269.ref013","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.pt.2017.04.001","article-title":"Brains and Brawn: Toxoplasma Infections of the Central Nervous System and Skeletal Muscle","volume":"33","author":"EA Wohlfert","year":"2017","journal-title":"Trends Parasitol"},{"issue":"4","key":"ppat.1012269.ref014","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1084\/jem.132.4.636","article-title":"The Toxoplasma gondii oocyst from cat feces","volume":"132","author":"JP Dubey","year":"1970","journal-title":"J Exp Med"},{"issue":"3","key":"ppat.1012269.ref015","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ijpara.2003.11.024","article-title":"Use of molecular and ultrastructural markers to evaluate stage conversion of Toxoplasma gondii in both the intermediate and definitive 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Zhu","year":"2022","journal-title":"Transbound Emerg Dis"},{"issue":"3","key":"ppat.1012269.ref019","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s10393-013-0859-x","article-title":"Toxoplasma gondii, source to sea: higher contribution of domestic felids to terrestrial parasite loading despite lower infection prevalence","volume":"10","author":"E Vanwormer","year":"2013","journal-title":"Ecohealth"},{"issue":"1","key":"ppat.1012269.ref020","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s12864-015-1225-x","article-title":"Asexual expansion of Toxoplasma gondii merozoites is distinct from tachyzoites and entails expression of non-overlapping gene families to attach, invade, and replicate within feline enterocytes","volume":"16","author":"AB Hehl","year":"2015","journal-title":"BMC Genomics"},{"issue":"4","key":"ppat.1012269.ref021","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/s41564-020-0674-4","article-title":"A MORC-driven 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cat-restricted Toxoplasma pre-sexual stages","volume":"625","author":"AV Antunes","year":"2024","journal-title":"Nature"},{"issue":"35","key":"ppat.1012269.ref028","doi-asserted-by":"crossref","first-page":"14311","DOI":"10.1074\/jbc.M117.792754","article-title":"Role of the E3 ubiquitin ligase RNF157 as a novel downstream effector linking PI3K and MAPK signaling pathways to the cell cycle","volume":"292","author":"T Dogan","year":"2017","journal-title":"J Biol Chem"},{"issue":"51","key":"ppat.1012269.ref029","doi-asserted-by":"crossref","first-page":"26399","DOI":"10.1074\/jbc.M116.717553","article-title":"E3 Ligase SCFbetaTrCP-induced DYRK1A Protein Degradation Is Essential for Cell Cycle Progression in HEK293 Cells","volume":"291","author":"Q Liu","year":"2016","journal-title":"J Biol Chem"},{"issue":"26","key":"ppat.1012269.ref030","doi-asserted-by":"crossref","first-page":"18514","DOI":"10.1074\/jbc.M114.559930","article-title":"SCF-FBXO31 E3 ligase targets DNA replication factor Cdt1 for proteolysis in the G2 phase of cell cycle to prevent re-replication","volume":"289","author":"P Johansson","year":"2014","journal-title":"J Biol Chem"},{"issue":"9","key":"ppat.1012269.ref031","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.1128\/MCB.21.9.3105-3117.2001","article-title":"Skp1p and the F-box protein Rcy1p form a non-SCF complex involved in recycling of the SNARE Snc1p in yeast","volume":"21","author":"JM Galan","year":"2001","journal-title":"Mol Cell Biol"},{"issue":"10","key":"ppat.1012269.ref032","doi-asserted-by":"crossref","first-page":"130131","DOI":"10.1098\/rsob.130131","article-title":"Beyond ubiquitination: the atypical functions of Fbxo7 and other F-box proteins","volume":"3","author":"DE Nelson","year":"2013","journal-title":"Open Biol"},{"issue":"4","key":"ppat.1012269.ref033","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nrc3700","article-title":"Roles of F-box proteins in cancer","volume":"14","author":"Z Wang","year":"2014","journal-title":"Nat Rev Cancer"},{"issue":"2","key":"ppat.1012269.ref034","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1093\/emboj\/17.2.368","article-title":"Association of human CUL-1 and ubiquitin-conjugating enzyme CDC34 with the F-box protein p45(SKP2): evidence for evolutionary conservation in the subunit composition of the CDC34-SCF pathway","volume":"17","author":"J Lisztwan","year":"1998","journal-title":"EMBO J"},{"issue":"8","key":"ppat.1012269.ref035","doi-asserted-by":"crossref","first-page":"6674","DOI":"10.1074\/jbc.M308875200","article-title":"The amino-terminal portion of the F-box protein Met30p mediates its nuclear import and assimilation into an SCF complex","volume":"279","author":"LE Brunson","year":"2004","journal-title":"J Biol Chem"},{"issue":"4","key":"ppat.1012269.ref036","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1111\/j.1365-313X.2003.01990.x","article-title":"GID2, an F-box subunit of the SCF E3 complex, specifically interacts with phosphorylated SLR1 protein and regulates the gibberellin-dependent degradation of SLR1 in rice","volume":"37","author":"K Gomi","year":"2004","journal-title":"Plant J"},{"issue":"25","key":"ppat.1012269.ref037","doi-asserted-by":"crossref","first-page":"10195","DOI":"10.1073\/pnas.0901864106","article-title":"JFK, a Kelch domain-containing F-box protein, links the SCF complex to p53 regulation","volume":"106","author":"L Sun","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1012269.ref038","doi-asserted-by":"crossref","first-page":"e1630","DOI":"10.1038\/cddis.2014.585","article-title":"F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7","volume":"6","author":"Y Liu","year":"2015","journal-title":"Cell Death Dis"},{"key":"ppat.1012269.ref039","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.biocel.2016.02.005","article-title":"Ubiquitination-mediated 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Biol"},{"issue":"Pt 23","key":"ppat.1012269.ref049","doi-asserted-by":"crossref","first-page":"5697","DOI":"10.1242\/jcs.01494","article-title":"Variability and heritability of cell division pathways in Toxoplasma gondii","volume":"117","author":"K Hu","year":"2004","journal-title":"J Cell Sci"},{"issue":"6","key":"ppat.1012269.ref050","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01846-17","article-title":"Ablation of an Ovarian Tumor Family Deubiquitinase Exposes the Underlying Regulation Governing the Plasticity of Cell Cycle Progression in Toxoplasma gondii","volume":"8","author":"A Dhara","year":"2017","journal-title":"MBio"},{"issue":"17","key":"ppat.1012269.ref051","doi-asserted-by":"crossref","first-page":"3320","DOI":"10.1242\/jcs.185223","article-title":"Apicoplast fatty acid synthesis is essential for pellicle formation at the end of cytokinesis in Toxoplasma gondii","volume":"129","author":"ES Martins-Duarte","year":"2016","journal-title":"J Cell 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regulatory hub of Cullin-RING ligases","volume":"48","author":"E Schulze-Niemand","year":"2023","journal-title":"Trends Biochem Sci"},{"issue":"9","key":"ppat.1012269.ref067","doi-asserted-by":"crossref","first-page":"e1008952","DOI":"10.1371\/journal.ppat.1008952","article-title":"COP9 signalosome is an essential and druggable parasite target that regulates protein degradation","volume":"16","author":"S Ghosh","year":"2020","journal-title":"PLoS Pathog"},{"issue":"9\u201310","key":"ppat.1012269.ref068","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.ejcb.2006.04.006","article-title":"The COP9 signalosome regulates cell proliferation of Dictyostelium discoideum","volume":"85","author":"D Rosel","year":"2006","journal-title":"Eur J Cell Biol"},{"issue":"3","key":"ppat.1012269.ref069","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.celrep.2012.08.019","article-title":"Structural basis for a reciprocal regulation between SCF and 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Sci"},{"issue":"7","key":"ppat.1012269.ref073","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/j.cell.2009.05.040","article-title":"SnapShot: F Box Proteins II","volume":"137","author":"JR Skaar","year":"2009","journal-title":"Cell"},{"issue":"2","key":"ppat.1012269.ref074","doi-asserted-by":"crossref","first-page":"e0060622","DOI":"10.1128\/msphere.00606-22","article-title":"Toxoplasma gondii AP2XII-2 Contributes to Transcriptional Repression for Sexual Commitment","volume":"8","author":"S Srivastava","year":"2023","journal-title":"mSphere"},{"issue":"2","key":"ppat.1012269.ref075","first-page":"167","article-title":"Ultrastructural study of early stages of asexual multiplication and microgametogony of Toxoplasma gondii in the small intestine of the cat","volume":"82","author":"DJ Ferguson","year":"1974","journal-title":"Acta Pathol Microbiol Scand B Microbiol Immunol"},{"key":"ppat.1012269.ref076","article-title":"Fussing About Fission: Defining Variety Among Mainstream and Exotic Apicomplexan Cell Division Modes","volume":"10","author":"M-J Gubbels","year":"2020","journal-title":"Frontiers in Cellular and Infection Microbiology"},{"issue":"35","key":"ppat.1012269.ref077","doi-asserted-by":"crossref","first-page":"26852","DOI":"10.1074\/jbc.M110.147041","article-title":"Toxoplasma gondii activates hypoxia-inducible factor (HIF) by stabilizing the HIF-1alpha subunit via type I activin-like receptor kinase receptor signaling","volume":"285","author":"M Wiley","year":"2010","journal-title":"J Biol Chem"},{"issue":"7","key":"ppat.1012269.ref078","doi-asserted-by":"crossref","first-page":"e1006483","DOI":"10.1371\/journal.ppat.1006483","article-title":"Checkpoints of apicomplexan cell division identified in Toxoplasma gondii","volume":"13","author":"CA Alvarez","year":"2017","journal-title":"PLoS 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Weber","year":"2012","journal-title":"Bioinformatics"},{"issue":"8","key":"ppat.1012269.ref082","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1038\/s41596-022-00710-w","article-title":"Using MetaboAnalyst 5.0 for LC-HRMS spectra processing, multi-omics integration and covariate adjustment of global metabolomics data","volume":"17","author":"Z Pang","year":"2022","journal-title":"Nat Protoc"},{"issue":"D1","key":"ppat.1012269.ref083","doi-asserted-by":"crossref","first-page":"D442","DOI":"10.1093\/nar\/gky1106","article-title":"The PRIDE database and related tools and resources in 2019: improving support for quantification data","volume":"47","author":"Y Perez-Riverol","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"19","key":"ppat.1012269.ref084","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"P Ewels","year":"2016","journal-title":"Bioinformatics"},{"issue":"4","key":"ppat.1012269.ref085","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: a fast spliced aligner with low memory requirements","volume":"12","author":"D Kim","year":"2015","journal-title":"Nat Methods"},{"issue":"12","key":"ppat.1012269.ref086","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"issue":"5","key":"ppat.1012269.ref087","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/s41564-023-01360-8","article-title":"Babesia duncani multi-omics identifies virulence factors and drug targets","volume":"8","author":"P Singh","year":"2023","journal-title":"Nat 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