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ATXN3 affects TP53
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ATXN3 binds TP53.
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ATXN3 binds TP53. 10 / 42
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"Liu et al. found that the pathological ATX3 binds to p53 with a stronger affinity compared to wild-type ATX3."
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"Ataxin-3 (ATXN3), a member of the MJD DUB family, also directly binds to native and polyubiquitinated TP53 and deubiquitinates and stabilizes TP53 by repressing its degradation through the ubiquitin–proteasome pathway [44]."
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"ATXN3 binds to p53, and further deubiquitinates, stabilizes p53 to regulate the functions of p53 in transactivation and apoptosis [ xref ]."
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"During deubiquitination process, ATX3 mainly associates with ubiquitinated p53 through its UIMs domain."
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"We observed a positive ATXN3-P53 protein correlation in HPV18 + AC, but not in HPV16 + SCC—likely due to HIF-1α-mediated suppression of P53 or HPV16 E6/E6AP-mediated P53 degradation[ xref , xref , xref ]."
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"Given that HPV E6/E7 oncoproteins promote P53 degradation, they may also influence the ATXN3-P53 axis [ xref , xref , xref ]."
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"Ataxin-3 (ATXN3), a member of the MJD DUB family, also directly binds to native and polyubiquitinated TP53 and deubiquitinates and stabilizes TP53 by repressing its degradation through the ubiquitin–proteasome pathway [ xref ]."
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"ATX-3 binds to native and polyubiquitinated p53 and deubiquitinates and stabilizes p53 by repressing its degradation through the ubiquitin (Ub)-proteasome pathway."
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Ubiquitinated TP53 binds ATXN3. 2 / 2
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"We have observed that the Josephin domain of ATX-3 is sufficient for the direct binding of ATX-3 to native p53, whereas the ubiquitinated p53 interacts with ATX-3 primarily through the UIMs, indicating that UIMs function to help recruit and bind the ubiquitinated p53 (XREF_FIG)."
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"Ataxin-3 (ATXN3), a member of the MJD DUB family, also directly binds to native and polyubiquitinated TP53 and deubiquitinates and stabilizes TP53 by repressing its degradation through the ubiquitin–proteasome pathway [44]."
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ATXN3 activates TP53.
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ATXN3 activates TP53. 10 / 22
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"Activation of p53 by mutant ataxin-3 is also related to phosphorylation of p53 at ser15 residue in the SCA3 transgenic mice model."
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"In cell and animal models of SCA3 induced by ataxin-3 mutation, mutant SCA3 can induce apoptosis of cerebellum and pons neurons by enhancing p53 transcriptional activity (Chou et al., 2011)."
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"These results suggest that ATX-3 deletion inhibits the stimulation of p53 transactivation activity."
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"Furthermore, to test whether mutant ATXN3 activates p53 and Chk2 via activating ATM, we pre-treated the cells with ATM inhibitor Ku55933 and expressed ATXN3-Q84 and assessed the activation of DNA damage response pathway."
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"These findings suggest that polyglutamine-expanded ataxin-3 enhances p53 transcriptional activity, which subsequently upregulates mRNA expression of pro-apoptotic Bax and PUMA.Mutant ataxin-3 enhancem[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"ATX-3 Promotes p53 Dependent Apoptosis in Cells and in Zebrafish."
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"Flow cytometry analysis using Annexin V-FITC and propidium iodide (PI) staining in HCT116 cells showed that knockdown of ATX-3 led to a decrease of camptothecin (CPT)-induced apoptosis, while ectopic expression of ATX-3 but not the catalytic inactive mutant ATX-3-C14A resulted in a significant increase of apoptosis in HCT116 p53 +/+ but not HCT116 p53 -/- cells (XREF_FIG), indicating that ATX-3 promoted p53 mediated apoptosis, which required its deubiquitinating enzymatic activity."
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"Using the zebrafish model system, we further examined whether ATX-3 induces p53 dependent apoptosis in vivo."
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"Deletion of ATXN3 resulted in destabilization of p53, whereas ectopic expression of ATXN3 induced expression of p53 target genes and promoted p53-dependent apoptosis."
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"When the FL ATX-3 mRNA was injected into WT but not the p53 mutant zebrafish embryos, significantly more apoptotic cells were observed in TUNEL staining assays, indicating that ATX-3 caused p53 dependent apoptosis in vivo."
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Mutated ATXN3 activates TP53. 10 / 10
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"Notably, compared with normal ataxin-3 protein, the gain-of-function mutant ataxin-3 triggers higher p53 protein and p53 responsive gene expression and causes more severe p53 dependent neurodegeneration in brain neuron cells of transgenic zebrafish and SCA3 mice 13."
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"Injection of mutant ATXN3 mRNA containing a CAG repeat expansion encoding ATXN3[80Q] caused p53-dependent apoptosis that was mainly detected in the head of the zebrafish at 24hpf, possibly indicating neuronal degeneration [71]."
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"Mutant ataxin-3 enhancement of p53 transcriptional activity is further supported by the finding that PUMA mRNA expression is upregulated in the cerebellum and pontine nuclei of SCA3 transgenic mice an[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In cell and animal models of SCA3 induced by ataxin-3 mutation, mutant SCA3 can induce apoptosis of cerebellum and pons neurons by enhancing p53 transcriptional activity (Chou et al., 2011)."
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"Knockdown of normal ATXN3 or PNKP, or expression of mutant ATXN3 increased the accumulation of DNA damage and persistent activation of the ATM and p53 dependent DNA repair pathway, suggesting ATXN3 may be a key regulator of PNKP dependent DNA repair."
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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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"Furthermore, to test whether mutant ATXN3 activates p53 and Chk2 via activating ATM, we pre-treated the cells with ATM inhibitor Ku55933 and expressed ATXN3-Q84 and assessed the activation of DNA damage response pathway."
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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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"Mutant ATXN3 activates the pro apoptotic p53 pathway by activating ATM in SCA3."
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"These results suggest that mutant ataxin-3 enhances p53 transcriptional activity by facilitating p53 phosphorylation at Ser15 residue.Our results suggest that one of molecular mechanisms underlying po[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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ATXN3 phosphorylates TP53.
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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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"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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"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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"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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ATXN3 leads to the phosphorylation of TP53. 1 / 1
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"Further studies are required to elucidate the exact mechanism by which polyglutamine-expanded ataxin-3 enhances p53 phosphorylation and activation in affected cerebellar and pontine nuclei neurons.SCA[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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ATXN3 deubiquitinates TP53.
1 | 3
ATXN3 deubiquitinates TP53. 4 / 4
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"Interestingly, polyQ expansion in Ataxin-3 increases the interaction and deubiquitination of p53, which is upregulated."
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"To determine whether ATX-3 can deubiquitinate p53 directly in vitro, we performed in vitro deubiquitination assays."
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"Thus, ATX-3 deubiquitinates and stabilizes p53 (XREF_FIG), which is an essential step for p53 function in cell cycle arrest and apoptosis (XREF_FIG)."
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"28801249"
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ATXN3 inhibits TP53.
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ATXN3 inhibits TP53. 1 / 3
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"ATX-3 deletion destabilizes p53, resulting in deficiency of p53 activity and functions, whereas ectopic expression of ATX-3 induces selective transcription and expression of p53 target genes and promotes p53 dependent apoptosis in both mammalian cells and the central nervous system of zebrafish."
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ATXN3 increases the amount of TP53.
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ATXN3 increases the amount of TP53. 2 / 2
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"Deletion of ATXN3 resulted in destabilization of p53, whereas ectopic expression of ATXN3 induced expression of p53 target genes and promoted p53-dependent apoptosis."
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"One can hypothesize that SCA3 and other neurodegenerative disorders involve a positive feedback between proteasomal degradation, aggregation, GSK3 activation, and increased p53 levels."
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ATXN3 ubiquitinates TP53.
| 1
Mutated ATXN3 leads to the ubiquitination of TP53. 1 / 1
| 1
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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."
29867345
ATXN3 decreases the amount of TP53.
| 1
Mutated ATXN3 decreases the amount of TP53. 1 / 1
| 1
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"Reducing p53 levels using transgenic RNAi did not alter the toxicity of mutant ataxin 3, as monitored by vacuole formation (XREF_SUPPLEMENTARY), consistent with specificity of the rescue of GFAP toxicity."
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TP53 affects ATXN3
5 | 17 17
TP53 binds ATXN3.
5 | 15 17
ATXN3 binds TP53. 10 / 42
5 | 13 17
sparser
"Liu et al. found that the pathological ATX3 binds to p53 with a stronger affinity compared to wild-type ATX3."
33425926
reach
"Ataxin-3 (ATXN3), a member of the MJD DUB family, also directly binds to native and polyubiquitinated TP53 and deubiquitinates and stabilizes TP53 by repressing its degradation through the ubiquitin–proteasome pathway [44]."
36551253
sparser
"ATXN3 binds to p53, and further deubiquitinates, stabilizes p53 to regulate the functions of p53 in transactivation and apoptosis [ xref ]."
37349820
sparser
"During deubiquitination process, ATX3 mainly associates with ubiquitinated p53 through its UIMs domain."
33425926
sparser
"We observed a positive ATXN3-P53 protein correlation in HPV18 + AC, but not in HPV16 + SCC—likely due to HIF-1α-mediated suppression of P53 or HPV16 E6/E6AP-mediated P53 degradation[ xref , xref , xref ]."
41507147
sparser
"Given that HPV E6/E7 oncoproteins promote P53 degradation, they may also influence the ATXN3-P53 axis [ xref , xref , xref ]."
41507147
sparser
"Ataxin-3 (ATXN3), a member of the MJD DUB family, also directly binds to native and polyubiquitinated TP53 and deubiquitinates and stabilizes TP53 by repressing its degradation through the ubiquitin–proteasome pathway [ xref ]."
36551253
sparser
"ATX-3 binds to native and polyubiquitinated p53 and deubiquitinates and stabilizes p53 by repressing its degradation through the ubiquitin (Ub)-proteasome pathway."
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No evidence text available
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Ubiquitinated TP53 binds ATXN3. 2 / 2
| 2
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"We have observed that the Josephin domain of ATX-3 is sufficient for the direct binding of ATX-3 to native p53, whereas the ubiquitinated p53 interacts with ATX-3 primarily through the UIMs, indicating that UIMs function to help recruit and bind the ubiquitinated p53 (XREF_FIG)."
27851749
reach
"Ataxin-3 (ATXN3), a member of the MJD DUB family, also directly binds to native and polyubiquitinated TP53 and deubiquitinates and stabilizes TP53 by repressing its degradation through the ubiquitin–proteasome pathway [44]."
36551253
TP53 activates ATXN3.
| 2
TP53 activates ATXN3. 2 / 2
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"Our data described in the present manuscript establish a mechanistic link between mutant ATXN3 expression and aberrant p53 pathway activation in SCA3, as previously reported [XREF_BIBR, XREF_BIBR]."
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"We report that persistent accumulation of DNA damage and strand breaks and chronic activation of the serine/threonine kinase ATM and the downstream p53 and protein kinase C-delta pro apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in SCA3."
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