{"id":{"repo_id":"nus","oai_identifier":"oai:scholarbank.nus.edu.sg:10635/28159"},"canonical_url":"https://search.dev.ndltd.org/etd/nus/oai:scholarbank.nus.edu.sg:10635/28159","repository":{"repo_id":"nus","name":"National University of Singapore","base_url":"https://scholarbank.nus.edu.sg/oai/request"},"display":{"title":"Transcriptional Regulation of the Inducible Costimulator (ICOS) in T Cells","abstract":"The inducible costimulator (ICOS) is a member of the CD28 family of costimulatory molecules and plays a central role in T-cell-mediated immunity. In this study, we investigated the molecular regulation of ICOS expression during early activation of CD4+ T cells by T cell receptor and CD28 co-engagement as well as during the differentiation of these cells into Th1 and Th2 lineages. In recently activated T cells, our data suggests that the Fyn-calcineurin-NFATc2 and MEK2-ERK1/2 signaling axes cooperate to transactivate icos transcription by acting on two different sites of its promoter. In T cells undergoing differentiation, we found that T-bet in Th1 or GATA-3 in Th2 cells could enhance, and NFATc2 could further synergize with either of them to increase, icos transcription via the icos promoter or a 3o \"UTR element respectively. Finally, we also found that ICOS is controlled at a post-transcriptional level by the RING-type E3 ubiquitin ligase, roquin.","abstract_html":"The inducible costimulator (ICOS) is a member of the CD28 family of costimulatory molecules and plays a central role in T-cell-mediated immunity. In this study, we investigated the molecular regulation of ICOS expression during early activation of CD4+ T cells by T cell receptor and CD28 co-engagement as well as during the differentiation of these cells into Th1 and Th2 lineages. In recently activated T cells, our data suggests that the Fyn-calcineurin-NFATc2 and MEK2-ERK1/2 signaling axes cooperate to transactivate icos transcription by acting on two different sites of its promoter. In T cells undergoing differentiation, we found that T-bet in Th1 or GATA-3 in Th2 cells could enhance, and NFATc2 could further synergize with either of them to increase, icos transcription via the icos promoter or a 3o "UTR element respectively. Finally, we also found that ICOS is controlled at a post-transcriptional level by the RING-type E3 ubiquitin ligase, roquin.","abstract_has_math":false,"creators":["TAN HEE MENG ANDY"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2008,"date_issued":"2008-03-19","date_published":"2008-03-19","updated_at":"2026-07-24T03:32:04Z","subjects":["inducible costimulator, T cell, T-bet, GATA-3, NFATc2, Th differentiation"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["TAN HEE MENG ANDY"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2008-03-19"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://scholarbank.nus.edu.sg/handle/10635/28159"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["inducible costimulator, T cell, T-bet, GATA-3, NFATc2, Th differentiation"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://scholarbank.nus.edu.sg/bitstreams/c716a853-7068-46fa-8061-b84ba3f84ef0/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The inducible costimulator (ICOS) is a member of the CD28 family of costimulatory molecules and plays a central role in T-cell-mediated immunity. In this study, we investigated the molecular regulation of ICOS expression during early activation of CD4+ T cells by T cell receptor and CD28 co-engagement as well as during the differentiation of these cells into Th1 and Th2 lineages. In recently activated T cells, our data suggests that the Fyn-calcineurin-NFATc2 and MEK2-ERK1/2 signaling axes cooperate to transactivate icos transcription by acting on two different sites of its promoter. In T cells undergoing differentiation, we found that T-bet in Th1 or GATA-3 in Th2 cells could enhance, and NFATc2 could further synergize with either of them to increase, icos transcription via the icos promoter or a 3o \"UTR element respectively. Finally, we also found that ICOS is controlled at a post-transcriptional level by the RING-type E3 ubiquitin ligase, roquin."]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["a17495b0cbf70e131bb494cb755fcf57","e0afd0e7d4f64427221d2fa83fd5e8a3"]},{"key":"dc:title","label":"Title","values":["Transcriptional Regulation of the Inducible Costimulator (ICOS) in T Cells"]}]}],"canonical_facts":{"dc:creator":["TAN HEE MENG ANDY"],"dc:date.issued":["2008-03-19"],"dc:description.abstract":["The inducible costimulator (ICOS) is a member of the CD28 family of costimulatory molecules and plays a central role in T-cell-mediated immunity. In this study, we investigated the molecular regulation of ICOS expression during early activation of CD4+ T cells by T cell receptor and CD28 co-engagement as well as during the differentiation of these cells into Th1 and Th2 lineages. In recently activated T cells, our data suggests that the Fyn-calcineurin-NFATc2 and MEK2-ERK1/2 signaling axes cooperate to transactivate icos transcription by acting on two different sites of its promoter. In T cells undergoing differentiation, we found that T-bet in Th1 or GATA-3 in Th2 cells could enhance, and NFATc2 could further synergize with either of them to increase, icos transcription via the icos promoter or a 3o \"UTR element respectively. 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