{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:45:49Z","timestamp":1787316349185,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012166","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000}}],"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006668","name":"Fondo para la Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2019-02900"],"award-info":[{"award-number":["PICT 2019-02900"]}],"id":[{"id":"10.13039\/501100006668","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Trypanosoma brucei<\/jats:italic>\n                    are protozoan parasites that cause sleeping sickness in humans and nagana in cattle. Inside the mammalian host, a quorum sensing-like mechanism coordinates its differentiation from a slender replicative form into a quiescent stumpy form, limiting growth and activating metabolic pathways that are beneficial to the parasite in the insect host. The post-translational modification of proteins with the Small Ubiquitin-like MOdifier (SUMO) enables dynamic regulation of cellular metabolism. SUMO can be conjugated to its targets as a monomer but can also form oligomeric chains. Here, we have investigated the role of SUMO chains in\n                    <jats:italic>T<\/jats:italic>\n                    .\n                    <jats:italic>brucei<\/jats:italic>\n                    by abolishing the ability of SUMO to polymerize. We have found that parasites able to conjugate only SUMO monomers are primed for differentiation. This was demonstrated for monomorphic lines that are normally unable to produce stumpy forms in response to quorum sensing signaling in mice, and also for pleomorphic cell lines in which stumpy cells were observed at unusually low parasitemia levels. SUMO chain mutants showed a stumpy compatible transcriptional profile and better competence to differentiate into procyclics. Our study indicates that SUMO depolymerization may represent a coordinated signal triggered during stumpy activation program.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012166","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T14:19:23Z","timestamp":1713449963000},"page":"e1012166","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Depolymerization of SUMO chains induces slender to stumpy differentiation in T. brucei bloodstream parasites"],"prefix":"10.1371","volume":"20","author":[{"given":"Paula Ana","family":"Iribarren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda Ayel\u00e9n","family":"Di Marzio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Agustina","family":"Berazategui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreu","family":"Saura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Coria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Cassataro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Rojas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Navarro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9890-6980","authenticated-orcid":true,"given":"Vanina Eder","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"issue":"10110","key":"ppat.1012166.ref001","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1016\/S0140-6736(17)31510-6","article-title":"Human African trypanosomiasis","volume":"390","author":"P. 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Rojas","year":"2019","journal-title":"Cell"},{"issue":"1","key":"ppat.1012166.ref007","doi-asserted-by":"crossref","first-page":"3322","DOI":"10.1038\/s41467-022-31057-1","article-title":"Extracellular release of two peptidases dominates generation of the trypanosome quorum-sensing signal.","volume":"13","author":"M.D. Tettey","year":"2022","journal-title":"Nat Commun"},{"issue":"24","key":"ppat.1012166.ref008","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abn2706","article-title":"A long noncoding RNA promotes parasite differentiation in African trypanosomes","volume":"8","author":"F. Guegan","year":"2022","journal-title":"Sci Adv"},{"issue":"3","key":"ppat.1012166.ref009","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.celrep.2016.09.041","article-title":"The AMPKalpha1 Pathway Positively Regulates the Developmental Transition from Proliferation to Quiescence in Trypanosoma brucei","volume":"17","author":"M. 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