IndraLab

Statements

Mutated ATXN3 phosphorylates TP53. 4 / 4
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"Not only in primary cultures of central nervous cells expressing mutant ataxin-3 but also in pontine nuclei of SCA3 transgenic mice, mutant ataxin-3 can increase the expression of total and phosphorylated p53 as well as the transcriptional activity of p53, which is associated with upregulation of Bax and activated caspase-3 and 9 expression and subsequent apoptotic cell death XREF_BIBR, XREF_BIBR."
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"Moreover, mutant ataxin-3 increases the phosphorylation of p53 and enhances the transcriptional activity of p53, which in turn amplifies pro apoptotic protein Bax expression in cultured cerebellar and pontine nuclei neurons XREF_BIBR, XREF_BIBR."
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"However, the mechanism by which mutant ATXN3 increases p53 phosphorylation and activates the p53 dependent pro apoptotic signaling pathways to facilitate neuronal death and dysfunction remains unknown."
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"For example, the HAT CBP also acts as a CREB binding protein and can take part in transcriptional dysfunction in HD, whereas post-translational modification affects transcriptional regulation, mutant ataxin-3 and mutant ataxin-7 could cause phosphorylation and ubiquitination of p53, resulting in p53 transcriptional regulation."
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