Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/72353
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dc.contributor.authorMuñoz, Úrsula-
dc.contributor.authorBartolomé Robledo, Fernando-
dc.contributor.authorBermejo-Pareja, Félix-
dc.contributor.authorMartín-Requero, Ángeles-
dc.date.issued2008-10-
dc.identifier.citationNeurobiology of Aging, 29 (10) : 1474-1484 (2008)es_ES
dc.identifier.issn0197-4580-
dc.identifier.urihttp://hdl.handle.net/10261/72353-
dc.description11 páginas, 11 figuras -- PAGS nros. 1474-1484es_ES
dc.description.abstractCyclin-dependent kinase inhibitor p27kip1 (p27), a critical determinant for cell cycle progression, is an important regulation target of mitogenic signals. We have recently reported the existence of a molecular link between decreased p27 levels and enhanced phosphorylation of pRb protein and proliferation of immortalized lymphocytes from Alzheimer's disease (AD) patients. These cell cycle disturbances might be considered systemic manifestations, which mirror changes thought to occur in the brain, where post-mitotic neurons have been shown to display various cell cycle markers prior to degeneration. This work was undertaken to delineate the molecular mechanisms underlying the p27 down-regulation associated with AD. To this end, we evaluated the p27 protein stability in control and AD lymphoblasts. Half-life of p27 protein was markedly reduced in lymphoblasts from AD patients compared with that in control cells. The increased phosphorylation of p27 at Thr187, rather than changes in the 26S proteasome activity, is likely responsible for the enhanced degradation of p27 in AD cells. The serum-induced enhanced proliferation of AD lymphoblasts and decreased levels of p27 were abrogated by calmodulin (CaM) antagonists. The findings presented here suggest that Ca2+/CaM-dependent overactivation of PI3K/Akt signaling cascade in AD cells, plays an important role in regulating p27 abundance by increasing its degradation in the ubiquitin-proteasome pathwayes_ES
dc.description.sponsorshipThis work has been supported by grants from the Spanish Fondo de Investigaciones Sanitarias (FIS PI040312). UM is a fellow from the Spanish Ministry of Education and Science, and FB holds a contract from the I3P program of the CSICes_ES
dc.language.isoenges_ES
dc.publisherElsevieres_ES
dc.rightsclosedAccesses_ES
dc.subjectAlzheimer's diseasees_ES
dc.subjectlymphocyteses_ES
dc.subjectCell proliferationes_ES
dc.subjectp27es_ES
dc.subjectproteasome activityes_ES
dc.subjectCalmodulines_ES
dc.subjectPI3K/Aktes_ES
dc.titleEnhanced proteasome-dependent degradation of the CDK inhibitor p27kip1 in immortalized lymphocytes from Alzheimer´s dementia patientses_ES
dc.typeartículoes_ES
dc.identifier.doi10.1016/j.neurobiolaging.2007.03.013-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1016/j.neurobiolaging.2007.03.013es_ES
dc.identifier.e-issn1558-1497-
item.grantfulltextnone-
item.cerifentitytypePublications-
item.openairetypeartículo-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextNo Fulltext-
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