Abstract
Ataxin-1 is a polyglutamine protein of unknown function that is encoded by the ATXN1 gene in humans. To gain insight into the function of ataxin-1, we sought to identify proteins that interact with ataxin-1 through yeast two-hybrid screening. In this study, transcriptional corepressor CtBP2 was identified as a protein that interacted with ataxin-1. CtBP2 and ataxin-1 colocalized in the nucleus of mammalian cells. Since the E-cadherin promoter is a target of CtBP-mediated repression, the relationship between ataxin-1 and the E-cadherin promoter was investigated. Chromatin immunoprecipitation assays showed that CtBP2 and ataxin-1 were recruited to the E-cadherin promoter in mammalian cells. Luciferase assays using E-cadherin promoter reporter constructs revealed that the luciferase activity was enhanced as the level of ataxin-1 protein expression increased. CtBP2 overexpression decreased E-cadherin expression, but expression of ataxin-1 inversely increased the mRNA and protein levels of endogenous E-cadherin. Interestingly, siRNA experiments showed that the transcriptional activation of ataxin-1 was associated with the presence of CtBP2. This study demonstrates that ataxin-1 occupies the promoter region of E-cadherin in vivo and that ataxin-1 activates the promoter in a CtBP2-mediated transcriptional regulation manner. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
Original language | English |
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Pages (from-to) | 713-722 |
Number of pages | 10 |
Journal | Biochimica et Biophysica Acta - Molecular Cell Research |
Volume | 1813 |
Issue number | 5 |
DOIs | |
State | Published - May 2011 |
Keywords
- Activation
- Ataxin-1
- CtBP2
- E-cadherin
- Repression