IndraLab

Statements

Mutated ATXN3 activates DNA damage checkpoint. 10 / 10
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"XREF_FIG), suggesting that mutant ATXN3 strongly activates the DNA damage response pathway and the polyQ sequence length is important for ATM pathway activation."
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", suggesting that the mutant ATXN3 induced DNA damage response ATM pathway activation is oxidation independent."
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"Either overexpression of PNKP or pharmacological inhibition of ATM in mutant ATXN3 expressing cells blocked aberrant activation of the pro death pathways and reduced cell death, suggesting that mutant ATXN3 mediated chronic activation of the DNA damage response ATM signaling pathway plays a pivotal role in neuronal dysfunction and neurodegeneration in SCA3."
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"XREF_FIG), suggesting that mutant ATXN3 strongly activates the DNA damage response pathway in vivo."
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"However, pre-treating cells with NAC did not block mutant ATXN3 mediated activation of the DNA damage response pathway (XREF_SUPPLEMENTARY Figs.)"
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"The amelioration of apoptosis by pharmacological inhibition of ATM and p53, suggest that mutant ATXN3 mediated aberrant activation of the DNA damage response pathway facilitates the apoptotic demise of neuronal cells in SCA3."
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"Likewise, expression of the mutant ATXN3 carrying 72 and 80 poly-glutamines (ATXN3-Q72 and ATXN3-Q80) in SH-SY5Y cells also strongly activated the DNA damage response ATM pathway (XREF_SUPPLEMENTARY)."
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"Mutant ATXN3 activates the DNA damage response pathway in SCA3."
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"Specific modulation of mutant ATXN3 mediated atypical activation of the DNA damage response p53 and PKCdelta pathways, or enhancing the efficacy of in vivo DNA damage repair may be effective strategies to combat the pathways leading to systemic neurodegeneration in SCA3."
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"Consistent with our hypothesis, ATXN3-Q84 expression failed to stimulate phosphorylation of Chk2 and p53 in the presence of the ATM inhibitor Ku55933 (XREF_SUPPLEMENTARY), substantiating our interpretation that mutant ATXN3 stimulates the DNA damage response p53 pathway via activating ATM."
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