{"id":{"repo_id":"bologna","oai_identifier":"oai:amsdottorato.cib.unibo.it:1074"},"canonical_url":"https://search.dev.ndltd.org/etd/bologna/oai:amsdottorato.cib.unibo.it:1074","repository":{"repo_id":"bologna","name":"Università di Bologna","base_url":"https://amsdottorato.unibo.it/cgi/oai2"},"display":{"title":"Ruolo della fosfolipasi C-β1 nel differenziamento miogenico: identificazione di nuovi target nucleari","abstract":"The expression of phospholipase C-β1 (PLC-β1) and cyclin D3 is highly induced during skeletal myoblast differentiation. We have previously shown that PLC-β1 activates cyclin D3 promoter during the differentiation of myoblasts to myotubes, indicating that PLC-β1 is a crucial regulator of mouse cyclin D3 gene. Here we report that PLC-β1 catalytic activity plays a role in the increase of cyclin D3 levels and in the induction of differentiation of C2C12 skeletal muscle cells. PLC-β1 mutational analysis revealed the importance of His331 and His378 for the catalytic activity. We show that following insulin administration, cyclin D3 mRNA levels are lower in cells overexpressing the PLC-β1 catalytically inactive form, as compared to wild type cells. We describe a novel signaling pathway elicited by PLC-β1 that modulates Activator Protein-1 (AP-1) activity. Indeed, gel mobility shift assays indicate that there is a c-jun binding site located in cyclin D3 promoter region specifically regulated by PLC-β1 and that c-jun binding activity is significantly increased by insulin stimulation and PLC-β1 overexpression. Moreover, mutation of c-jun/AP-1 binding site decreases the basal cyclin D3 promoter activity and eliminates its induction by insulin and PLC-β1 overexpression. Interestingly, we observed that the ectopic expression of the Inositol Polyphosphate Multikinase (IPMK) in C2C12 myoblasts enhances cyclin D3 gene expression and that the mutation of c-jun site in cyclin D3 promoter determines an impairment of IPMK-dependent promoter induction. These results indicate that PLC-β1 activates a c-jun/AP-1 target gene, i.e. cyclin D3, during myogenic differentiation through IPMK signaling.","abstract_html":"The expression of phospholipase C-β1 (PLC-β1) and cyclin D3 is highly induced during skeletal myoblast differentiation. We have previously shown that PLC-β1 activates cyclin D3 promoter during the differentiation of myoblasts to myotubes, indicating that PLC-β1 is a crucial regulator of mouse cyclin D3 gene. Here we report that PLC-β1 catalytic activity plays a role in the increase of cyclin D3 levels and in the induction of differentiation of C2C12 skeletal muscle cells. PLC-β1 mutational analysis revealed the importance of His331 and His378 for the catalytic activity. We show that following insulin administration, cyclin D3 mRNA levels are lower in cells overexpressing the PLC-β1 catalytically inactive form, as compared to wild type cells. We describe a novel signaling pathway elicited by PLC-β1 that modulates Activator Protein-1 (AP-1) activity. Indeed, gel mobility shift assays indicate that there is a c-jun binding site located in cyclin D3 promoter region specifically regulated by PLC-β1 and that c-jun binding activity is significantly increased by insulin stimulation and PLC-β1 overexpression. Moreover, mutation of c-jun/AP-1 binding site decreases the basal cyclin D3 promoter activity and eliminates its induction by insulin and PLC-β1 overexpression. Interestingly, we observed that the ectopic expression of the Inositol Polyphosphate Multikinase (IPMK) in C2C12 myoblasts enhances cyclin D3 gene expression and that the mutation of c-jun site in cyclin D3 promoter determines an impairment of IPMK-dependent promoter induction. These results indicate that PLC-β1 activates a c-jun/AP-1 target gene, i.e. cyclin D3, during myogenic differentiation through IPMK signaling.","abstract_has_math":false,"creators":["Ramazzotti, Giulia <1978>"],"institution":"Alma Mater Studiorum - Università di Bologna","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Manzoli, Lucia"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2008,"date_issued":"2008-05-26","date_published":"2008-05-26","updated_at":"2026-07-24T01:12:07Z","subjects":["BIO/16 Anatomia umana"],"languages":["it"],"rights":["info:eu-repo/semantics/openAccess"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["urn:nbn:it:unibo-1042"],"render_values":[{"text":"urn:nbn:it:unibo-1042","href":null,"code":true}]}]},"links":{"outbound_url":"https://doi.org/10.6092/unibo/amsdottorato/1074.","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Manzoli, Lucia"]},{"key":"dc:creator","label":"Author","values":["Ramazzotti, Giulia <1978>"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2008-05-26"]},{"key":"dc:publisher","label":"Institution","values":["Alma Mater Studiorum - Università di Bologna"]},{"key":"dc:relation","label":"Dc Relation","values":["https://amsdottorato.unibo.it/id/eprint/1074/"]},{"key":"dc:type","label":"Dc Type","values":["Doctoral Thesis","PeerReviewed"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["BIO/16 Anatomia umana"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["it"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://amsdottorato.unibo.it/id/eprint/1074/1/Tesi_Ramazzotti_Giulia.pdf","urn:nbn:it:unibo-1042","Ramazzotti, Giulia (2008) Ruolo della fosfolipasi C-β1 nel differenziamento miogenico: identificazione di nuovi target nucleari, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Scienze morfologiche umane e molecolari <https://amsdottorato.unibo.it/view/dottorati/DOT332/>, 20 Ciclo. DOI 10.6092/unibo/amsdottorato/1074."]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The expression of phospholipase C-β1 (PLC-β1) and cyclin D3 is highly induced during skeletal myoblast differentiation. We have previously shown that PLC-β1 activates cyclin D3 promoter during the differentiation of myoblasts to myotubes, indicating that PLC-β1 is a crucial regulator of mouse cyclin D3 gene. Here we report that PLC-β1 catalytic activity plays a role in the increase of cyclin D3 levels and in the induction of differentiation of C2C12 skeletal muscle cells. PLC-β1 mutational analysis revealed the importance of His331 and His378 for the catalytic activity. We show that following insulin administration, cyclin D3 mRNA levels are lower in cells overexpressing the PLC-β1 catalytically inactive form, as compared to wild type cells. We describe a novel signaling pathway elicited by PLC-β1 that modulates Activator Protein-1 (AP-1) activity. Indeed, gel mobility shift assays indicate that there is a c-jun binding site located in cyclin D3 promoter region specifically regulated by PLC-β1 and that c-jun binding activity is significantly increased by insulin stimulation and PLC-β1 overexpression. Moreover, mutation of c-jun/AP-1 binding site decreases the basal cyclin D3 promoter activity and eliminates its induction by insulin and PLC-β1 overexpression. Interestingly, we observed that the ectopic expression of the Inositol Polyphosphate Multikinase (IPMK) in C2C12 myoblasts enhances cyclin D3 gene expression and that the mutation of c-jun site in cyclin D3 promoter determines an impairment of IPMK-dependent promoter induction. These results indicate that PLC-β1 activates a c-jun/AP-1 target gene, i.e. cyclin D3, during myogenic differentiation through IPMK signaling."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Ruolo della fosfolipasi C-β1 nel differenziamento miogenico: identificazione di nuovi target nucleari"]}]}],"canonical_facts":{"dc:contributor":["Manzoli, Lucia"],"dc:creator":["Ramazzotti, Giulia <1978>"],"dc:date":["2008-05-26"],"dc:description":["The expression of phospholipase C-β1 (PLC-β1) and cyclin D3 is highly induced during skeletal myoblast differentiation. We have previously shown that PLC-β1 activates cyclin D3 promoter during the differentiation of myoblasts to myotubes, indicating that PLC-β1 is a crucial regulator of mouse cyclin D3 gene. Here we report that PLC-β1 catalytic activity plays a role in the increase of cyclin D3 levels and in the induction of differentiation of C2C12 skeletal muscle cells. PLC-β1 mutational analysis revealed the importance of His331 and His378 for the catalytic activity. We show that following insulin administration, cyclin D3 mRNA levels are lower in cells overexpressing the PLC-β1 catalytically inactive form, as compared to wild type cells. We describe a novel signaling pathway elicited by PLC-β1 that modulates Activator Protein-1 (AP-1) activity. Indeed, gel mobility shift assays indicate that there is a c-jun binding site located in cyclin D3 promoter region specifically regulated by PLC-β1 and that c-jun binding activity is significantly increased by insulin stimulation and PLC-β1 overexpression. Moreover, mutation of c-jun/AP-1 binding site decreases the basal cyclin D3 promoter activity and eliminates its induction by insulin and PLC-β1 overexpression. Interestingly, we observed that the ectopic expression of the Inositol Polyphosphate Multikinase (IPMK) in C2C12 myoblasts enhances cyclin D3 gene expression and that the mutation of c-jun site in cyclin D3 promoter determines an impairment of IPMK-dependent promoter induction. These results indicate that PLC-β1 activates a c-jun/AP-1 target gene, i.e. cyclin D3, during myogenic differentiation through IPMK signaling."],"dc:format":["application/pdf"],"dc:identifier":["https://amsdottorato.unibo.it/id/eprint/1074/1/Tesi_Ramazzotti_Giulia.pdf","urn:nbn:it:unibo-1042","Ramazzotti, Giulia (2008) Ruolo della fosfolipasi C-β1 nel differenziamento miogenico: identificazione di nuovi target nucleari, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Scienze morfologiche umane e molecolari <https://amsdottorato.unibo.it/view/dottorati/DOT332/>, 20 Ciclo. DOI 10.6092/unibo/amsdottorato/1074."],"dc:language":["it"],"dc:publisher":["Alma Mater Studiorum - Università di Bologna"],"dc:relation":["https://amsdottorato.unibo.it/id/eprint/1074/"],"dc:rights":["info:eu-repo/semantics/openAccess"],"dc:subject":["BIO/16 Anatomia umana"],"dc:title":["Ruolo della fosfolipasi C-β1 nel differenziamento miogenico: identificazione di nuovi target nucleari"],"dc:type":["Doctoral Thesis","PeerReviewed"]},"updated_at":"2026-07-24T01:12:07Z"}