{"id":{"repo_id":"york","oai_identifier":"oai:yorkspace.library.yorku.ca:10315/35022"},"canonical_url":"https://search.dev.ndltd.org/etd/york/oai:yorkspace.library.yorku.ca:10315/35022","repository":{"repo_id":"york","name":"York University","base_url":"https://yorkspace.library.yorku.ca/oai/request"},"display":{"title":"The Role of CDCA7 in Akt-mediated Myc-Dependent Apoptosis and Proliferation","abstract":"CDCA7, or cell division cycle associated protein A7, was described in 2001 by Prescott and colleagues as a target of Myc-dependent transcriptional regulation (Prescott et al., 2001). We have identified CDCA7 as associating with the transcription factor Myc and is the target of phosphorylation by the prosurvival serine/threonine kinase Akt. Phosphorylation by Akt at threonine 163 disrupts CDCA7 association with Myc, promotes binding to 14-3-3 and sequestration in the cytoplasm. Coexpression of CDCA7 and Myc in fibroblasts potentiates Myc-dependent apoptosis upon serum withdrawal. In contrast, knockdown of CDCA7 by shRNA abrogated Myc-dependent apoptosis. Myc induced transformation of fibroblasts was reduced in the presence of CDCA7 and significantly inhibited by the expression of the non-Myc binding mutant (156-187) CDCA7. We have shown that CDCA7 enhances the activation of an E-box in a Myc-binding dependent manner. CDCA7 increases Myc occupancy of the proapoptotic BAX promoter, elevates BAX and Cyclin B1 mRNA levels while reducing p15INK4B mRNA levels. This data points to a novel mechanism which implicates Akt phosphorylation of CDCA7 as participating in the dual signal model of Myc of function and thus affecting Myc-dependent growth and transformation. In this study, we have also shown that expression of CDCA7 reduces proliferation rates and shifts cell cycle distribution towards G2/M phase and that phosphorylation of CDCA7 at T163 occurs strictly in G2/M. CDCA7 phosphorylated at threonine 163 colocalizes with the centrosomal protein marker -Tubulin and activated Akt (phospho-serine 473) in mitotic cells. Finally, we have shown that CDCA7 co-associates with monomers of itself which is dependent on amino acids 187-234, adding to the possible mechanisms by which CDCA7 function may be regulated.","abstract_html":"CDCA7, or cell division cycle associated protein A7, was described in 2001 by Prescott and colleagues as a target of Myc-dependent transcriptional regulation (Prescott et al., 2001). We have identified CDCA7 as associating with the transcription factor Myc and is the target of phosphorylation by the prosurvival serine/threonine kinase Akt. Phosphorylation by Akt at threonine 163 disrupts CDCA7 association with Myc, promotes binding to 14-3-3 and sequestration in the cytoplasm. Coexpression of CDCA7 and Myc in fibroblasts potentiates Myc-dependent apoptosis upon serum withdrawal. In contrast, knockdown of CDCA7 by shRNA abrogated Myc-dependent apoptosis. Myc induced transformation of fibroblasts was reduced in the presence of CDCA7 and significantly inhibited by the expression of the non-Myc binding mutant (156-187) CDCA7. We have shown that CDCA7 enhances the activation of an E-box in a Myc-binding dependent manner. CDCA7 increases Myc occupancy of the proapoptotic BAX promoter, elevates BAX and Cyclin B1 mRNA levels while reducing p15INK4B mRNA levels. This data points to a novel mechanism which implicates Akt phosphorylation of CDCA7 as participating in the dual signal model of Myc of function and thus affecting Myc-dependent growth and transformation. In this study, we have also shown that expression of CDCA7 reduces proliferation rates and shifts cell cycle distribution towards G2/M phase and that phosphorylation of CDCA7 at T163 occurs strictly in G2/M. CDCA7 phosphorylated at threonine 163 colocalizes with the centrosomal protein marker -Tubulin and activated Akt (phospho-serine 473) in mitotic cells. Finally, we have shown that CDCA7 co-associates with monomers of itself which is dependent on amino acids 187-234, adding to the possible mechanisms by which CDCA7 function may be regulated.","abstract_has_math":false,"creators":["Gabor, Tim Vincent"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Scheid, Michael P."],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-08-27","date_published":"2018-08-27","updated_at":"2026-07-24T06:33:53Z","subjects":["Biochemistry"],"languages":["en"],"rights":["Author owns copyright, except where explicitly noted. Please contact the author directly with licensing requests."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10315/35022","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Scheid, Michael P."]},{"key":"dc:creator","label":"Author","values":["Gabor, Tim Vincent"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2018-08-27T16:42:37Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2018-08-27T16:42:37Z"]},{"key":"dc:date.issued","label":"Date","values":["2018-08-27"]},{"key":"dc:type","label":"Dc Type","values":["Electronic Thesis or Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biochemistry"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Author owns copyright, except where explicitly noted. Please contact the author directly with licensing requests."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10315/35022"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["CDCA7, or cell division cycle associated protein A7, was described in 2001 by Prescott and colleagues as a target of Myc-dependent transcriptional regulation (Prescott et al., 2001). We have identified CDCA7 as associating with the transcription factor Myc and is the target of phosphorylation by the prosurvival serine/threonine kinase Akt. Phosphorylation by Akt at threonine 163 disrupts CDCA7 association with Myc, promotes binding to 14-3-3 and sequestration in the cytoplasm. Coexpression of CDCA7 and Myc in fibroblasts potentiates Myc-dependent apoptosis upon serum withdrawal. In contrast, knockdown of CDCA7 by shRNA abrogated Myc-dependent apoptosis. Myc induced transformation of fibroblasts was reduced in the presence of CDCA7 and significantly inhibited by the expression of the non-Myc binding mutant (156-187) CDCA7. We have shown that CDCA7 enhances the activation of an E-box in a Myc-binding dependent manner. CDCA7 increases Myc occupancy of the proapoptotic BAX promoter, elevates BAX and Cyclin B1 mRNA levels while reducing p15INK4B mRNA levels. This data points to a novel mechanism which implicates Akt phosphorylation of CDCA7 as participating in the dual signal model of Myc of function and thus affecting Myc-dependent growth and transformation. In this study, we have also shown that expression of CDCA7 reduces proliferation rates and shifts cell cycle distribution towards G2/M phase and that phosphorylation of CDCA7 at T163 occurs strictly in G2/M. CDCA7 phosphorylated at threonine 163 colocalizes with the centrosomal protein marker -Tubulin and activated Akt (phospho-serine 473) in mitotic cells. Finally, we have shown that CDCA7 co-associates with monomers of itself which is dependent on amino acids 187-234, adding to the possible mechanisms by which CDCA7 function may be regulated."]},{"key":"dc:title","label":"Title","values":["The Role of CDCA7 in Akt-mediated Myc-Dependent Apoptosis and Proliferation"]}]}],"canonical_facts":{"dc:contributor.advisor":["Scheid, Michael P."],"dc:creator":["Gabor, Tim Vincent"],"dc:date.accessioned":["2018-08-27T16:42:37Z"],"dc:date.available":["2018-08-27T16:42:37Z"],"dc:date.issued":["2018-08-27"],"dc:description.abstract":["CDCA7, or cell division cycle associated protein A7, was described in 2001 by Prescott and colleagues as a target of Myc-dependent transcriptional regulation (Prescott et al., 2001). We have identified CDCA7 as associating with the transcription factor Myc and is the target of phosphorylation by the prosurvival serine/threonine kinase Akt. Phosphorylation by Akt at threonine 163 disrupts CDCA7 association with Myc, promotes binding to 14-3-3 and sequestration in the cytoplasm. Coexpression of CDCA7 and Myc in fibroblasts potentiates Myc-dependent apoptosis upon serum withdrawal. In contrast, knockdown of CDCA7 by shRNA abrogated Myc-dependent apoptosis. Myc induced transformation of fibroblasts was reduced in the presence of CDCA7 and significantly inhibited by the expression of the non-Myc binding mutant (156-187) CDCA7. We have shown that CDCA7 enhances the activation of an E-box in a Myc-binding dependent manner. CDCA7 increases Myc occupancy of the proapoptotic BAX promoter, elevates BAX and Cyclin B1 mRNA levels while reducing p15INK4B mRNA levels. This data points to a novel mechanism which implicates Akt phosphorylation of CDCA7 as participating in the dual signal model of Myc of function and thus affecting Myc-dependent growth and transformation. In this study, we have also shown that expression of CDCA7 reduces proliferation rates and shifts cell cycle distribution towards G2/M phase and that phosphorylation of CDCA7 at T163 occurs strictly in G2/M. CDCA7 phosphorylated at threonine 163 colocalizes with the centrosomal protein marker -Tubulin and activated Akt (phospho-serine 473) in mitotic cells. Finally, we have shown that CDCA7 co-associates with monomers of itself which is dependent on amino acids 187-234, adding to the possible mechanisms by which CDCA7 function may be regulated."],"dc:identifier.uri":["http://hdl.handle.net/10315/35022"],"dc:language.iso":["en"],"dc:rights":["Author owns copyright, except where explicitly noted. Please contact the author directly with licensing requests."],"dc:subject":["Biochemistry"],"dc:title":["The Role of CDCA7 in Akt-mediated Myc-Dependent Apoptosis and Proliferation"],"dc:type":["Electronic Thesis or Dissertation"]},"updated_at":"2026-07-24T06:33:53Z"}