{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T02:26:18Z","timestamp":1783131978996,"version":"3.54.6"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In the early phase of infection, the intramacrophage pathogen Leishmania donovani protects its niche with the help of the antiapoptotic protein myeloid cell leukemia-1 (MCL-1). Whether Leishmania could exploit MCL-1, an extremely labile protein, at the late phase is still unclear. A steady translational level of MCL-1 observed up to 48 h postinfection and increased caspase-3 activity in MCL-1\u2013silenced infected macrophages documented its importance in the late hours of infection. The transcript level of MCL-1 showed a sharp decline at 6 h postinfection, and persistent MCL-1 expression in cyclohexamide-treated cells negates the possibility of de novo protein synthesis, thereby suggesting infection-induced stability. Increased ubiquitination, a prerequisite for proteasomal degradation of MCL-1, was also found to be absent in the late hours of infection. Lack of interaction with its specific E3 ubiquitin ligase MULE (MCL-1 ubiquitin ligase E3) and specific deubiquitinase USP9X prompted us to search for blockade of the ubiquitin-binding site in MCL-1. To this end, TCTP (translationally controlled tumor protein), a well-known binding partner of MCL-1 and antiapoptotic regulator, was found to be strongly associated with MCL-1 during infection. Phosphorylation of TCTP, a requirement for MCL-1 binding, was also increased in infected macrophages. Knockdown of TCTP decreased MCL-1 expression and short hairpin RNA\u2013mediated silencing of TCTP in an infected mouse model of visceral leishmaniasis showed decreased parasite burden and induction of liver cell apoptosis. Collectively, our investigation revealed a key mechanism of how L. donovani exploits TCTP to establish infection within the host.<\/jats:p>","DOI":"10.4049\/jimmunol.2100748","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T19:20:52Z","timestamp":1657740052000},"page":"2540-2548","source":"Crossref","is-referenced-by-count":10,"title":["Translationally Controlled Tumor Protein\u2013Mediated Stabilization of Host Antiapoptotic Protein MCL-1 Is Critical for Establishment of Infection by Intramacrophage Parasite <i>Leishmania donovani<\/i>"],"prefix":"10.1093","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2688-7274","authenticated-orcid":false,"given":"Jayeeta","family":"Giri","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Calcutta , Kolkata,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6691-5279","authenticated-orcid":false,"given":"Moumita","family":"Basu","sequence":"additional","affiliation":[{"name":"Biosciences and Bioengineering Department, Indian Institute of Technology , Mumbai,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Calcutta , Kolkata,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0968-5654","authenticated-orcid":false,"given":"Tarun","family":"Mishra","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Indian Institute of Science Education and Research Bhopal , Bhopal,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4748-253X","authenticated-orcid":false,"given":"Kuladip","family":"Jana","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Bose Institute, P1\/12 Calcutta Improvement Trust Scheme VIIM , Kolkata,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2210-5180","authenticated-orcid":false,"given":"Ajit","family":"Chande","sequence":"additional","affiliation":[{"name":"Molecular Virology Laboratory, Indian Institute of Science Education and Research Bhopal , Bhopal,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1102-9437","authenticated-orcid":false,"given":"Anindita","family":"Ukil","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Calcutta , Kolkata,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,6,1]]},"reference":[{"key":"2025021009070568700_r1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1189\/jlb.1001877","article-title":"Leishmania major-mediated prevention of programmed cell death induction in infected macrophages is associated with the repression of mitochondrial release of cytochrome c","volume":"76","author":"Akarid","year":"2004","journal-title":"J. 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