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https://hdl.handle.net/1822/67549
Título: | Absence of ataxin-3 leads to cytoskeletal disorganization and increased cell death |
Autor(es): | Rodrigues, Ana João Costa, Maria do Carmo Silva, Teresa L Ferreira, Daniela Bajanca, Fernanda Santos, Elsa Clara Carvalho Logarinho Maciel, P. |
Palavras-chave: | 3T3 Cells Animals Apoptosis Ataxin-3 Blotting, Western Cell Cycle Cytoskeleton Focal adhesions HeLa Cells Humans In situ nick-end labeling Integrin alpha1 Mice Microscopy, Confocal Nerve tissue proteins Nuclear proteins RNA interference Repressor proteins Reverse transcriptase polymerase chain reaction Transcription factors Polyglutamine Ubiquitin-proteasome Sinocerebellar ataxia type 3 Tubulin |
Data: | Out-2010 |
Editora: | Elsevier |
Revista: | Biochimica et Biophysica Acta (BBA). Molecular Cell Research |
Resumo(s): | Ataxin-3 (ATXN3) is a widely expressed protein that binds to ubiquitylated proteins, has deubiquitylating activity in vitro and is thought to modulate substrate degradation through the ubiquitin-proteasome pathway. Expansion of a polyglutamine tract in ATXN3 causes Machado-Joseph disease, a late-onset neurodegenerative disorder characterized by ubiquitin-positive aggregate formation and specific neuronal death. Although ATXN3 has been involved in transcriptional repression and in the ubiquitin-proteasome pathway, its biological function is still unknown. In this work, we show that depletion of ATXN3 using small-interference RNA (siRNA) causes a prominent phenotype in both human and mouse cell lines. A mild increase in ubiquitylation occurs and cells exhibit ubiquitin-positive foci, which is consistent with ATXN3 putative function as a deubiquitylating enzyme. In addition, siATXN3-silenced cells exhibit marked morphological changes such as rounder shape and loss of adhesion protrusions. At a structural level, the microtubule, microfilament and intermediate filament networks are severely compromised and disorganized. This cytoskeletal phenotype is reversible and dependent on ATXN3 levels. Cell-extracellular matrix connection is also affected in ATXN3-depleted cells as talin expression is reduced in the focal adhesions and lower levels of alpha-1 integrin subunit are expressed at their surface. Although the cytoskeletal and adhesion problems do not originate any major change in the cell cycle of siATXN3-depleted cells, cell death is increased in siATXN3 cultures compared to controls. In summary, in this work we show that the absence of ATXN3 leads to an overt cytoskeletal/adhesion defect raising the possibility that this protein may play a role in the cytoskeleton. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/67549 |
DOI: | 10.1016/j.bbamcr.2010.07.004 |
ISSN: | 0167-4889 |
e-ISSN: | 1879-2596 |
Versão da editora: | https://www.sciencedirect.com/science/article/pii/S0167488910001989?via%3Dihub |
Arbitragem científica: | yes |
Acesso: | Acesso restrito autor |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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rodrigues2010.pdf Acesso restrito! | 1,27 MB | Adobe PDF | Ver/Abrir |