{"id":{"repo_id":"vcu","oai_identifier":"oai:scholarscompass.vcu.edu:etd-2159"},"canonical_url":"https://search.dev.ndltd.org/etd/vcu/oai:scholarscompass.vcu.edu:etd-2159","repository":{"repo_id":"vcu","name":"Virginia Commonwealth University","base_url":"https://scholarscompass.vcu.edu/do/oai/"},"display":{"title":"Role of MDM2 In Cell Growth Regulation","abstract":"MDM2 has been shown to induce G0-Gl/S phase arrest. To determine the cell cycle step targeted by MDM2, flow cytometry was employed to detect induction of events during the G1-S phase transition in MDM2-arrested cells. MDM2 overexpression does not prevent expression of cyclin D, cyclin D-CDK mediated phosphorylation of Rb or cyclin E in normal, immortal or tumor-derived cells. However, MDM2 down-regulates cyclin A expression specifically in normal cells, which is associated with G1 arrest. The domain of MDM2 capable of this function is located within its N-terminal 58-109 amino acids. To down-regulate cyclin A, MDM2 requires a functional pl6/Brg 1 pathway, as silencing of either of these proteins disables this function of MDM2. Bromodeoxyuridine incorporation studies suggest that another inhibitory domain, ID2, inhibits DNA replication, while an MDM2 deletion mutant containing the N-terminal 1-220 amino acids including inhibitory domain ID1 does not effectively prevent BrdU incorporation in an immortal cell line that is non-responsive to growth arrest by the cyclin A inhibitory domain. This suggests that induction of MDM2 leads to G1 arrest by at least two independent mechanisms, and multiple genetic damages are necessary to overcome MDM2-mediated growth arrest. To determine novel interacting partners of MDM2, proteomic analysis of MDM2 overexpressed in tumor-derived H1299 cells was carried out. This analysis revealed interaction of MDM2 with the translation elongation factor efl-α, and was validated by immunoprecipitation and Western blotting and shown to colocalize with MDM2 in the cytoplasm. To interact with efl-α, MDM2 was determined to require two domains, one of which is located within amino acids 221-325 and another within the N-terminal 58 amino acids of MDM2.","abstract_html":"MDM2 has been shown to induce G0-Gl/S phase arrest. To determine the cell cycle step targeted by MDM2, flow cytometry was employed to detect induction of events during the G1-S phase transition in MDM2-arrested cells. MDM2 overexpression does not prevent expression of cyclin D, cyclin D-CDK mediated phosphorylation of Rb or cyclin E in normal, immortal or tumor-derived cells. However, MDM2 down-regulates cyclin A expression specifically in normal cells, which is associated with G1 arrest. The domain of MDM2 capable of this function is located within its N-terminal 58-109 amino acids. To down-regulate cyclin A, MDM2 requires a functional pl6/Brg 1 pathway, as silencing of either of these proteins disables this function of MDM2. Bromodeoxyuridine incorporation studies suggest that another inhibitory domain, ID2, inhibits DNA replication, while an MDM2 deletion mutant containing the N-terminal 1-220 amino acids including inhibitory domain ID1 does not effectively prevent BrdU incorporation in an immortal cell line that is non-responsive to growth arrest by the cyclin A inhibitory domain. This suggests that induction of MDM2 leads to G1 arrest by at least two independent mechanisms, and multiple genetic damages are necessary to overcome MDM2-mediated growth arrest. To determine novel interacting partners of MDM2, proteomic analysis of MDM2 overexpressed in tumor-derived H1299 cells was carried out. This analysis revealed interaction of MDM2 with the translation elongation factor efl-α, and was validated by immunoprecipitation and Western blotting and shown to colocalize with MDM2 in the cytoplasm. To interact with efl-α, MDM2 was determined to require two domains, one of which is located within amino acids 221-325 and another within the N-terminal 58 amino acids of MDM2.","abstract_has_math":false,"creators":["Frum, Rebecca Anne"],"institution":null,"degree_name":"Doctor of Philosophy","degree_level":"Dissertation","degree_discipline":"Biochemistry","degree_department":null,"school":null,"contributors":["Dr. Swati Palit Deb"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2006,"date_issued":"2006-01-01T08:00:00Z","date_published":"2006-01-01T08:00:00Z","updated_at":"2026-07-24T05:54:53Z","subjects":["oncogene","carcinoma","cancer","oncoprotein","cell interaction","Biochemistry, Biophysics, and Structural Biology","Life Sciences"],"languages":[],"rights":["© The Author"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarscompass.vcu.edu/etd/1160"],"render_values":[{"text":"https://scholarscompass.vcu.edu/etd/1160","href":"https://scholarscompass.vcu.edu/etd/1160","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.25772/RFJJ-A657","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Dr. Swati Palit Deb"]},{"key":"dc:creator","label":"Author","values":["Frum, Rebecca Anne"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2014-07-09T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["oncogene","carcinoma","cancer","oncoprotein","cell interaction","Biochemistry, Biophysics, and Structural Biology","Life Sciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["© The Author"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.25772/RFJJ-A657","https://scholarscompass.vcu.edu/etd/1160"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["MDM2 has been shown to induce G0-Gl/S phase arrest. To determine the cell cycle step targeted by MDM2, flow cytometry was employed to detect induction of events during the G1-S phase transition in MDM2-arrested cells. MDM2 overexpression does not prevent expression of cyclin D, cyclin D-CDK mediated phosphorylation of Rb or cyclin E in normal, immortal or tumor-derived cells. However, MDM2 down-regulates cyclin A expression specifically in normal cells, which is associated with G1 arrest. The domain of MDM2 capable of this function is located within its N-terminal 58-109 amino acids. To down-regulate cyclin A, MDM2 requires a functional pl6/Brg 1 pathway, as silencing of either of these proteins disables this function of MDM2. Bromodeoxyuridine incorporation studies suggest that another inhibitory domain, ID2, inhibits DNA replication, while an MDM2 deletion mutant containing the N-terminal 1-220 amino acids including inhibitory domain ID1 does not effectively prevent BrdU incorporation in an immortal cell line that is non-responsive to growth arrest by the cyclin A inhibitory domain. This suggests that induction of MDM2 leads to G1 arrest by at least two independent mechanisms, and multiple genetic damages are necessary to overcome MDM2-mediated growth arrest. To determine novel interacting partners of MDM2, proteomic analysis of MDM2 overexpressed in tumor-derived H1299 cells was carried out. This analysis revealed interaction of MDM2 with the translation elongation factor efl-α, and was validated by immunoprecipitation and Western blotting and shown to colocalize with MDM2 in the cytoplasm. To interact with efl-α, MDM2 was determined to require two domains, one of which is located within amino acids 221-325 and another within the N-terminal 58 amino acids of MDM2."]},{"key":"dc:title","label":"Title","values":["Role of MDM2 In Cell Growth Regulation"]}]}],"canonical_facts":{"dc:contributor":["Dr. Swati Palit Deb"],"dc:creator":["Frum, Rebecca Anne"],"dc:date.available":["2014-07-09T07:00:00Z"],"dc:description.abstract":["MDM2 has been shown to induce G0-Gl/S phase arrest. To determine the cell cycle step targeted by MDM2, flow cytometry was employed to detect induction of events during the G1-S phase transition in MDM2-arrested cells. MDM2 overexpression does not prevent expression of cyclin D, cyclin D-CDK mediated phosphorylation of Rb or cyclin E in normal, immortal or tumor-derived cells. However, MDM2 down-regulates cyclin A expression specifically in normal cells, which is associated with G1 arrest. The domain of MDM2 capable of this function is located within its N-terminal 58-109 amino acids. To down-regulate cyclin A, MDM2 requires a functional pl6/Brg 1 pathway, as silencing of either of these proteins disables this function of MDM2. Bromodeoxyuridine incorporation studies suggest that another inhibitory domain, ID2, inhibits DNA replication, while an MDM2 deletion mutant containing the N-terminal 1-220 amino acids including inhibitory domain ID1 does not effectively prevent BrdU incorporation in an immortal cell line that is non-responsive to growth arrest by the cyclin A inhibitory domain. This suggests that induction of MDM2 leads to G1 arrest by at least two independent mechanisms, and multiple genetic damages are necessary to overcome MDM2-mediated growth arrest. To determine novel interacting partners of MDM2, proteomic analysis of MDM2 overexpressed in tumor-derived H1299 cells was carried out. This analysis revealed interaction of MDM2 with the translation elongation factor efl-α, and was validated by immunoprecipitation and Western blotting and shown to colocalize with MDM2 in the cytoplasm. To interact with efl-α, MDM2 was determined to require two domains, one of which is located within amino acids 221-325 and another within the N-terminal 58 amino acids of MDM2."],"dc:identifier":["https://doi.org/10.25772/RFJJ-A657","https://scholarscompass.vcu.edu/etd/1160"],"dc:rights":["© The Author"],"dc:subject":["oncogene","carcinoma","cancer","oncoprotein","cell interaction","Biochemistry, Biophysics, and Structural Biology","Life Sciences"],"dc:title":["Role of MDM2 In Cell Growth Regulation"],"thesis:degree_discipline":["Biochemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy"]},"updated_at":"2026-07-24T05:54:53Z"}