Artículo
Glycogen Synthase Kinase-3-ß (GSK3ß) negatively regulates PTTG1/human Securin protein stability, and GSK3ß inactivation correlates with securin accumulation in breast tumors.
Autor/es | Mora Santos, María del Mar
Limón Mortés, María Cristina Giráldez Macías, Servando Herrero Ruiz, Joaquín Sáez, Carmen Japón Rodríguez, Miguel Ángel Tortolero García, María Dolores Romero Portillo, Francisco |
Fecha de publicación | 2011 |
Fecha de depósito | 2022-01-12 |
Publicado en |
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Resumen | PTTG1, also known as securin, is an inactivating partner of separase, the major effector for chromosome segregation during mitosis. At the metaphase-to-anaphase transition, securin is targeted for proteasomal destruction ... PTTG1, also known as securin, is an inactivating partner of separase, the major effector for chromosome segregation during mitosis. At the metaphase-to-anaphase transition, securin is targeted for proteasomal destruction by the anaphase-promoting complex or cyclosome, allowing activation of separase. In addition, securin is overexpressed in metastatic or genomically instable tumors, suggesting a relevant role for securin in tumor progression. Stability of securin is regulated by phosphorylation; some phosphorylated forms are degraded out of mitosis, by the action of the SKP1-CUL1-F-box protein (SCF) complex. The kinases targeting securin for proteolysis have not been identified, and mechanistic insight into the cause of securin accumulation in human cancers is lacking. Here, we demonstrate that glycogen synthase kinase-3β (GSK3β) phosphorylates securin to promote its proteolysis via SCF(βTrCP) E3 ubiquitin ligase. Importantly, a strong correlation between securin accumulation and GSK3β inactivation was observed in breast cancer tissues, indicating that GSK3β inactivation may account for securin accumulation in breast cancers. |
Agencias financiadoras | Ministerio de Ciencia e Innovación (MICIN). España Ministerio de Sanidad. España European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) Junta de Andalucía |
Identificador del proyecto | SAF2008-03095
SAF2008-05046 ISCIII-RETIC-RD06/0020-FEDER P08-CVI-03603 PI09-0589 |
Cita | Mora Santos, M.d.M., Limón Mortés, M.C., Giráldez Macías, S., Herrero Ruiz, J., Sáez, C., Japón Rodríguez, M.Á.,...,Romero Portillo, F. (2011). Glycogen Synthase Kinase-3-ß (GSK3ß) negatively regulates PTTG1/human Securin protein stability, and GSK3ß inactivation correlates with securin accumulation in breast tumors.. The Journal Of Biological Chemistry, 286 (34), 30047-30056. |
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