Encontrados 8 documentos, a visualizar página 1 de 1
FoxM1 repression during human aging leads to mitotic decline and aneuploidy-dri...
Macedo, Joana Catarina; Vaz, Sara; Bakker, Bjorn; Ribeiro, Rui; Bakker, Petra Lammigje; Escandell, Jose Miguel; Ferreira, Miguel Godinho; Medema, RenéAneuploidy, an abnormal chromosome number, has been linked to aging and age-associated diseases, but the underlying molecular mechanisms remain unknown. Here we show, through direct live-cell imaging of young, middle-aged, and old-aged primary human dermal fibroblasts, that aneuploidy increases with aging due to general dysfunction of the mitotic machinery. Increased chromosome mis-segregation in elderly mitoti...
Dominant negative effect of polyglutamine expansion perturbs normal function of...
Carvalho, Andreia Alexandra Neves; Logarinho, Elsa; Freitas, Ana; Silva, Sara Duarte; Costa, Maria do Carmo; Fernandes, Anabela SilvaThe physiological function of Ataxin-3 (ATXN3), a deubiquitylase (DUB) involved in Machado–Joseph Disease (MJD), remains elusive. In this study, we demonstrate that ATXN3 is required for neuronal differentiation and for normal cell morphology, cytoskeletal organization, proliferation and survival of SH-SY5Y and PC12 cells. This cellular phenotype is associated with increased proteasomal degradation of a5 integr...
Absence of ataxin-3 leads to enhanced stress response in C. elegans
Rodrigues, Ana João; Carvalho, Andreia Neves; Castro, Andreia Cristiana Teixeira de; Rokka, Anne; Corthals, Gary; Logarinho, Elsa; Maciel, P.Ataxin-3, the protein involved in Machado-Joseph disease, is able to bind ubiquitylated substrates and act as a deubiquitylating enzyme in vitro, and it has been involved in the modulation of protein degradation by the ubiquitinproteasome pathway. C. elegans and mouse ataxin-3 knockout models are viable and without any obvious phenotype in a basal condition however their phenotype in stress situations has never...
Ataxin-3 plays a role in mouse myogenic differentiation through regulation of i...
Costa, Maria do Carmo; Bajanca, Fernanda; Rodrigues, Ana João; Tomé, Ricardo J.; Corthals, Gary; Ribeiro, Sandra Macedo; Paulson, Henry L.BACKGROUND: During myogenesis several transcription factors and regulators of protein synthesis and assembly are rapidly degraded by the ubiquitin-proteasome system (UPS). Given the potential role of the deubiquitinating enzyme (DUB) ataxin-3 in the UPS, and the high expression of the murine ataxin-3 homolog in muscle during embryogenesis, we sought to define its role in muscle differentiation. METHODOLOGY/PRIN...
IFN-gamma-dependent activation of macrophages during experimental infections by...
Torrado, Egídio; Fraga, Alexandra Gabriel; Logarinho, Elsa; Martins, Teresa G.; Carmona, Jenny A.; Gama, José B.; Carvalho, Maria A.Buruli ulcer, caused by Mycobacterium ulcerans infections, is a necrotizing skin disease whose pathogenesis is associated with the exotoxin mycolactone. Despite the relevance of this emergent disease, little is known on the immune response against the pathogen. Following the recent demonstration of an intramacrophage growth phase for M. ulcerans, we investigated the biological relevance of IFN-gamma and the ant...
The human spindle assembly checkpoint protein Bub3 is required for the establis...
Logarinho, Elsa; Resende, Tatiana; Torres, C.; Bousbaa, HassanThe spindle assembly checkpoint monitors the status of kinetochore–microtubule (K-MT) attachments and delays anaphase onset until full metaphase alignment is achieved. Recently, the role of spindle assembly checkpoint proteins was expanded with the discovery that BubR1 and Bub1 are implicated in the regulation of K-MT attachments. One unsolved question is whether Bub3, known to form cell cycle constitutive comp...
Kinetochore-microtubule interactions "in check" by Bub1, Bub3 and BubR1: the du...
Logarinho, Elsa; Bousbaa, HassanThe spindle assembly checkpoint (SAC) prevents anaphase onset until all chromosomes accomplish proper bipolar attachments to the mitotic spindle and come under tension, thereby ensuring the fidelity of chromosome segregation. Despite significant advances in our understanding of SAC signalling, a clear link between checkpoint signalling and the molecular mechanisms underlying chromosome attachment to microtubule...
NEDD8: A new ataxin-3 interactor
Ferro, Anabela; Carvalho, Ana Luísa; Teixeira-Castro, Andreia; Almeida, Carla; Tomé, Ricardo J.; Cortes, Luísa; Rodrigues, Ana-João; Logarinho, ElsaMachado-Joseph disease (MJD/SCA3) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG tract in the coding portion of the ATXN3 gene. The presence of ubiquitin-positive aggregates of the defective protein in affected neurons is characteristic of this and most of the polyglutamine disorders. Recently, the accumulation of the neural precursor cell expressed developmentally downregul...