{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/28865"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/28865","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"Regulation of tumor necrosis factor-alpha induced apoptosis via posttranslational modifications in a human colon adenocarcinoma cell line","abstract":"(cont.) phosphoproteomics technology, IMAC/LC/MS/MS, [approximately] 200 phosphosites were identified from HT-29 cells, some of which were detected only from insulin-treated cells. Our phosphoproteomics approach also enabled us to detect alteration of both known and unknown phosphorylation states of apoptosis-related proteins at two time points during early apoptosis induced by tumor necrosis factor-α","abstract_html":"(cont.) phosphoproteomics technology, IMAC/LC/MS/MS, [approximately] 200 phosphosites were identified from HT-29 cells, some of which were detected only from insulin-treated cells. Our phosphoproteomics approach also enabled us to detect alteration of both known and unknown phosphorylation states of apoptosis-related proteins at two time points during early apoptosis induced by tumor necrosis factor-α","abstract_has_math":false,"creators":["Kim, Ji-Eun, 1974-"],"institution":"Massachusetts Institute of Technology","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Massachusetts Institute of Technology. Biological Engineering Division.","school":null,"contributors":[],"advisors":["Steven R. Tannenbaum."],"committee_chairs":[],"committee_members":[],"year":2004,"date_issued":"2004","date_published":"2004","updated_at":"2026-07-22T22:21:02Z","subjects":["Biological Engineering Division."],"languages":["en_US"],"rights":["MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission."],"rights_urls":["http://dspace.mit.edu/handle/1721.1/7582"],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1721.1/28865","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Steven R. Tannenbaum."]},{"key":"dc:contributor.department","label":"Department","values":["Massachusetts Institute of Technology. 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They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission."]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://dspace.mit.edu/handle/1721.1/7582"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1721.1/28865"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2004.","Includes bibliographical references."]},{"key":"dc:description.abstract","label":"Abstract","values":["(cont.) phosphoproteomics technology, IMAC/LC/MS/MS, [approximately] 200 phosphosites were identified from HT-29 cells, some of which were detected only from insulin-treated cells. Our phosphoproteomics approach also enabled us to detect alteration of both known and unknown phosphorylation states of apoptosis-related proteins at two time points during early apoptosis induced by tumor necrosis factor-α","Apoptosis, a physiologically regulated cell death, plays critical roles in development and immune system by maintaining tissue homeostasis. The thesis project investigates regulations of apoptosis in a human colon adenocarcinoma cell line, HT-29, exposed to diverse cellular stimuli, focusing on a specific protein as well as global level of proteins. The first part of the thesis demonstrated S-nitrosation of procaspase-9. S-nitrosation is a novel protein modification to regulate protein-protein interaction or protein activity. This modification has been implied to inactivate caspases. We could visualize S-nitrosation of an initiator caspase, procaspase-9, by enriching low-abundant procaspase-9 with immunoprecipitation and stabilizing S-nitroso-cysteine with biotin labeling. Nitric oxide synthase inhibitors and tumor necrosis factor-α (TNF-α) reduced the S-nitrosation level of procaspase-9, suggesting that S-nitrosation may be regulated by a nitric oxide synthase and denitrosation is likely a mechanism of apoptosis. The second part of the thesis is to examine survival effects of insulin on cells undergoing TNF-α-induced apoptosis. Insulin decreased the TNF-α-induced cleavage of key apoptotic mediators, caspases, and their substrates as well as apoptosis, in part, depending on phosphatidylinositol-3 kinase (PI-3K)/Akt pathway. One of protective mechanisms by insulin is likely to decrease the TNF-α-induced dissociation of a potent inhibitor of caspases, X-chromosome linked inhibitor of apoptosis protein (XIAP), from procaspase-9 via PI-3K/Akt pathway. Lack of phosphoproteomics data in HT-29 cells led the third part of the thesis to focus on investigating global level regulation of phosphoproteins during apoptosis. With a"]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph.D."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Regulation of tumor necrosis factor-alpha induced apoptosis via posttranslational modifications in a human colon adenocarcinoma cell line"]}]}],"canonical_facts":{"dc:contributor.advisor":["Steven R. Tannenbaum."],"dc:contributor.department":["Massachusetts Institute of Technology. Biological Engineering Division."],"dc:contributor.other":["Massachusetts Institute of Technology. Biological Engineering Division."],"dc:creator":["Kim, Ji-Eun, 1974-"],"dc:date.accessioned":["2005-09-27T18:46:07Z"],"dc:date.available":["2005-09-27T18:46:07Z"],"dc:date.issued":["2004"],"dc:description":["Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2004.","Includes bibliographical references."],"dc:description.abstract":["(cont.) phosphoproteomics technology, IMAC/LC/MS/MS, [approximately] 200 phosphosites were identified from HT-29 cells, some of which were detected only from insulin-treated cells. Our phosphoproteomics approach also enabled us to detect alteration of both known and unknown phosphorylation states of apoptosis-related proteins at two time points during early apoptosis induced by tumor necrosis factor-α","Apoptosis, a physiologically regulated cell death, plays critical roles in development and immune system by maintaining tissue homeostasis. The thesis project investigates regulations of apoptosis in a human colon adenocarcinoma cell line, HT-29, exposed to diverse cellular stimuli, focusing on a specific protein as well as global level of proteins. The first part of the thesis demonstrated S-nitrosation of procaspase-9. S-nitrosation is a novel protein modification to regulate protein-protein interaction or protein activity. This modification has been implied to inactivate caspases. We could visualize S-nitrosation of an initiator caspase, procaspase-9, by enriching low-abundant procaspase-9 with immunoprecipitation and stabilizing S-nitroso-cysteine with biotin labeling. Nitric oxide synthase inhibitors and tumor necrosis factor-α (TNF-α) reduced the S-nitrosation level of procaspase-9, suggesting that S-nitrosation may be regulated by a nitric oxide synthase and denitrosation is likely a mechanism of apoptosis. The second part of the thesis is to examine survival effects of insulin on cells undergoing TNF-α-induced apoptosis. Insulin decreased the TNF-α-induced cleavage of key apoptotic mediators, caspases, and their substrates as well as apoptosis, in part, depending on phosphatidylinositol-3 kinase (PI-3K)/Akt pathway. One of protective mechanisms by insulin is likely to decrease the TNF-α-induced dissociation of a potent inhibitor of caspases, X-chromosome linked inhibitor of apoptosis protein (XIAP), from procaspase-9 via PI-3K/Akt pathway. Lack of phosphoproteomics data in HT-29 cells led the third part of the thesis to focus on investigating global level regulation of phosphoproteins during apoptosis. With a"],"dc:description.degree":["Ph.D."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["http://hdl.handle.net/1721.1/28865"],"dc:language.iso":["en_US"],"dc:publisher":["Massachusetts Institute of Technology"],"dc:rights":["MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission."],"dc:rights.uri":["http://dspace.mit.edu/handle/1721.1/7582"],"dc:subject":["Biological Engineering Division."],"dc:title":["Regulation of tumor necrosis factor-alpha induced apoptosis via posttranslational modifications in a human colon adenocarcinoma cell line"],"dc:type":["Thesis"]},"updated_at":"2026-07-22T22:21:02Z"}