{"id":{"repo_id":"utmb","oai_identifier":"oai:utmb-ir.tdl.org:2152.3/676"},"canonical_url":"https://search.dev.ndltd.org/etd/utmb/oai:utmb-ir.tdl.org:2152.3/676","repository":{"repo_id":"utmb","name":"University of Texas Medical Branch","base_url":"https://utmb-ir.tdl.org/server/oai/request"},"display":{"title":"Study on the Physical and Functional Interaction between Fortilin and Peroxiredoxin I","abstract":"Apoptosis or programmed cell death is a highly regulated cellular process which is essential for the development of an organism as well as for tissue and organ maintenance. Dysregulation of apoptosis is responsible for a variety of disease phenotypes from cancer to neurodegenerative and cardiovascular diseases. Fortilin (FT) is an anti-apoptotic protein that prevents apoptotic cell death under various conditions of cellular stress including UV, chemical and oxidative stress. However, the molecular mechanism of this pro-survival action under conditions of oxidative stress has yet to be elucidated. Using an immunoprecipitation and mass spectrometry-based screening approach, we identified a number of potential fortilin interacting proteins, including the anti-oxidant enzyme peroxiredoxin I (Prx I). Prx I is a thioredoxin-dependent peroxidase enzyme that is known to be protective against reactive oxygen species (ROS)-induced cell death. We confirmed the interaction between FT and Prx I by using various approaches, including reverse co-immunoprecipitation, direct binding and co-localization studies in cultured cells as well as animal tissue and demonstrated that FT stabilizes Prx I in U2OS cells by preventing its proteasomal degradation. Furthermore, our results showed that wild type FT, but not a point mutant of FT that does not bind to Prx I, enhances the enzymatic activity of Prx I. Further investigations revealed that FT inhibits the deactivating phosphorylation of Prx I by the serine/threonine kinase Mst1 in a dose-dependent manner. Additionally, the anti-apoptotic activity of FT under oxidative stress was found to be dependent on its interaction with Prx I. Finally, we demonstrated that a liver-specific knockout of FT exacerbates ethanol-induced oxidative liver damage. Taken together, our data confirm a novel interaction between FT and Prx I that positively regulates the functions of both proteins, leading to increased cytoprotection and may be explored in future as a therapeutic target in oxidative stress-induced pathological conditions.","abstract_html":"Apoptosis or programmed cell death is a highly regulated cellular process which is essential for the development of an organism as well as for tissue and organ maintenance. Dysregulation of apoptosis is responsible for a variety of disease phenotypes from cancer to neurodegenerative and cardiovascular diseases. Fortilin (FT) is an anti-apoptotic protein that prevents apoptotic cell death under various conditions of cellular stress including UV, chemical and oxidative stress. However, the molecular mechanism of this pro-survival action under conditions of oxidative stress has yet to be elucidated. Using an immunoprecipitation and mass spectrometry-based screening approach, we identified a number of potential fortilin interacting proteins, including the anti-oxidant enzyme peroxiredoxin I (Prx I). Prx I is a thioredoxin-dependent peroxidase enzyme that is known to be protective against reactive oxygen species (ROS)-induced cell death. We confirmed the interaction between FT and Prx I by using various approaches, including reverse co-immunoprecipitation, direct binding and co-localization studies in cultured cells as well as animal tissue and demonstrated that FT stabilizes Prx I in U2OS cells by preventing its proteasomal degradation. Furthermore, our results showed that wild type FT, but not a point mutant of FT that does not bind to Prx I, enhances the enzymatic activity of Prx I. Further investigations revealed that FT inhibits the deactivating phosphorylation of Prx I by the serine/threonine kinase Mst1 in a dose-dependent manner. Additionally, the anti-apoptotic activity of FT under oxidative stress was found to be dependent on its interaction with Prx I. Finally, we demonstrated that a liver-specific knockout of FT exacerbates ethanol-induced oxidative liver damage. Taken together, our data confirm a novel interaction between FT and Prx I that positively regulates the functions of both proteins, leading to increased cytoprotection and may be explored in future as a therapeutic target in oxidative stress-induced pathological conditions.","abstract_has_math":false,"creators":["Chattopadhyay, Abhijnan"],"institution":"The University of Texas Medical Branch at Galveston","degree_name":"Biochemistry and Molecular Biology (Doctoral)","degree_level":"Doctoral","degree_discipline":"Biochemistry and Molecular Biology","degree_department":null,"school":null,"contributors":[],"advisors":["Srivastava, Satish K"],"committee_chairs":[],"committee_members":["Fujise, Kenichi","Boehning, Darren F","Pazdrak, Konrad","McConnell, Bradley K"],"year":null,"date_issued":"","date_published":null,"updated_at":"2026-07-24T05:51:01Z","subjects":["apoptosis","oxidative stress","fortilin","peroxiredoxin I","enzyme activity","phosphorylation","Mst1"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2152.3/676","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Srivastava, Satish K"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Fujise, Kenichi","Boehning, Darren F","Pazdrak, Konrad","McConnell, Bradley K"]},{"key":"dc:creator","label":"Author","values":["Chattopadhyay, Abhijnan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2016-05-05T21:35:59Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2016-05-05T21:35:59Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry and Molecular Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Biochemistry and Molecular Biology (Doctoral)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas Medical Branch at Galveston"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["apoptosis","oxidative stress","fortilin","peroxiredoxin I","enzyme activity","phosphorylation","Mst1"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/2152.3/676"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Apoptosis or programmed cell death is a highly regulated cellular process which is essential for the development of an organism as well as for tissue and organ maintenance. Dysregulation of apoptosis is responsible for a variety of disease phenotypes from cancer to neurodegenerative and cardiovascular diseases. Fortilin (FT) is an anti-apoptotic protein that prevents apoptotic cell death under various conditions of cellular stress including UV, chemical and oxidative stress. However, the molecular mechanism of this pro-survival action under conditions of oxidative stress has yet to be elucidated. Using an immunoprecipitation and mass spectrometry-based screening approach, we identified a number of potential fortilin interacting proteins, including the anti-oxidant enzyme peroxiredoxin I (Prx I). Prx I is a thioredoxin-dependent peroxidase enzyme that is known to be protective against reactive oxygen species (ROS)-induced cell death. We confirmed the interaction between FT and Prx I by using various approaches, including reverse co-immunoprecipitation, direct binding and co-localization studies in cultured cells as well as animal tissue and demonstrated that FT stabilizes Prx I in U2OS cells by preventing its proteasomal degradation. Furthermore, our results showed that wild type FT, but not a point mutant of FT that does not bind to Prx I, enhances the enzymatic activity of Prx I. Further investigations revealed that FT inhibits the deactivating phosphorylation of Prx I by the serine/threonine kinase Mst1 in a dose-dependent manner. Additionally, the anti-apoptotic activity of FT under oxidative stress was found to be dependent on its interaction with Prx I. Finally, we demonstrated that a liver-specific knockout of FT exacerbates ethanol-induced oxidative liver damage. Taken together, our data confirm a novel interaction between FT and Prx I that positively regulates the functions of both proteins, leading to increased cytoprotection and may be explored in future as a therapeutic target in oxidative stress-induced pathological conditions."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Study on the Physical and Functional Interaction between Fortilin and Peroxiredoxin I"]}]}],"canonical_facts":{"dc:contributor.advisor":["Srivastava, Satish K"],"dc:contributor.committeemember":["Fujise, Kenichi","Boehning, Darren F","Pazdrak, Konrad","McConnell, Bradley K"],"dc:creator":["Chattopadhyay, Abhijnan"],"dc:date.accessioned":["2016-05-05T21:35:59Z"],"dc:date.available":["2016-05-05T21:35:59Z"],"dc:description.abstract":["Apoptosis or programmed cell death is a highly regulated cellular process which is essential for the development of an organism as well as for tissue and organ maintenance. Dysregulation of apoptosis is responsible for a variety of disease phenotypes from cancer to neurodegenerative and cardiovascular diseases. Fortilin (FT) is an anti-apoptotic protein that prevents apoptotic cell death under various conditions of cellular stress including UV, chemical and oxidative stress. However, the molecular mechanism of this pro-survival action under conditions of oxidative stress has yet to be elucidated. Using an immunoprecipitation and mass spectrometry-based screening approach, we identified a number of potential fortilin interacting proteins, including the anti-oxidant enzyme peroxiredoxin I (Prx I). Prx I is a thioredoxin-dependent peroxidase enzyme that is known to be protective against reactive oxygen species (ROS)-induced cell death. We confirmed the interaction between FT and Prx I by using various approaches, including reverse co-immunoprecipitation, direct binding and co-localization studies in cultured cells as well as animal tissue and demonstrated that FT stabilizes Prx I in U2OS cells by preventing its proteasomal degradation. Furthermore, our results showed that wild type FT, but not a point mutant of FT that does not bind to Prx I, enhances the enzymatic activity of Prx I. Further investigations revealed that FT inhibits the deactivating phosphorylation of Prx I by the serine/threonine kinase Mst1 in a dose-dependent manner. Additionally, the anti-apoptotic activity of FT under oxidative stress was found to be dependent on its interaction with Prx I. Finally, we demonstrated that a liver-specific knockout of FT exacerbates ethanol-induced oxidative liver damage. Taken together, our data confirm a novel interaction between FT and Prx I that positively regulates the functions of both proteins, leading to increased cytoprotection and may be explored in future as a therapeutic target in oxidative stress-induced pathological conditions."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["http://hdl.handle.net/2152.3/676"],"dc:subject":["apoptosis","oxidative stress","fortilin","peroxiredoxin I","enzyme activity","phosphorylation","Mst1"],"dc:title":["Study on the Physical and Functional Interaction between Fortilin and Peroxiredoxin I"],"dc:type":["Thesis"],"thesis:degree_discipline":["Biochemistry and Molecular Biology"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Biochemistry and Molecular Biology (Doctoral)"],"thesis:institution_name":["The University of Texas Medical Branch at Galveston"]},"updated_at":"2026-07-24T05:51:01Z"}