IndraLab

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ATXN3 inhibits PNKP. 6 / 8
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"Diminished PNKP activity results in persistent accumulation of DNA strand breaks, leading to chronic activation of the DNA damage response ataxia telangiectasia mutated (ATM) protein kinase and the downstream pro apoptotic p53 dependent signaling pathways in SCA3."
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"Hence, PNKP inactivation by expanded ataxin-3 may serve an important role in SCA3 pathogenesis, especially given the fact that the nervous system is particularly sensitive to DNA damage compared to other tissues xref ."
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"Hence, PNKP inactivation by expanded ataxin-3 may serve an important role in SCA3 pathogenesis, especially given the fact that the nervous system is particularly sensitive to DNA damage compared to other tissues XREF_BIBR."
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"Recently, two research teams reported the interaction between ATX3 and PNKP, and discovered that polyQ expanded ATX3 inactivates PNKP phosphatase activity, causing persistent DNA damage and chronic activation of pro apoptotic signaling, which leads to SCA3 pathogenesis."
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"It has been suggested that the PNKP inactivation by mutant ataxin-3 might in part be explained by its recruitment in polyQ aggregates xref ."
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"We have shown previously that ATXN3 depleted or pathogenic ATXN3 expressing cells abrogate polynucleotide kinase 3 '-phosphatase (PNKP) activity."
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