IndraLab

Statements

ATXN3 affects TP53
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ATXN3 binds TP53.
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TP53 binds ATXN3. 10 / 40
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"Li-Fraumeni syndrome (LFS) is an autosomal dominant disease that is associated with germline TP53 mutations and it predisposes affected individuals to a high risk of developing multiple tumors."
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"We wonder whether the polyQ expansion affects the ATX-3 and p53 interaction."
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"We have found that ATX-3 interacts with p53 and functions as a novel p53 DUB."
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sparser
"Therefore, both the Josephin and UIM domain coordinately regulate the interaction between ATX-3 and p53 ( xref )."
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"The interaction between ATX-3 and p53 was confirmed under physiological condition ( xref ) and with in vitro purified forms ( xref ), indicating a direct association between these two proteins."
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biogrid
No evidence text available
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"Consistently, as shown in xref , the cysteine 14 mutation did not affect the binding of ATX-3 to either native or ubiquitinated p53, whereas the ΔN mutant lost its binding to both forms of p53."
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"Instructively, mutations effecting the expression of p53 are associated with Li Fraumini syndrome, an autosomal dominant hereditary cancer predisoposition syndrome."
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"As ATX-3 interacts with p53 under physiological conditions and regulates the ubiquitination of p53 in cells, it is possible that ATX-3 may regulate the turnover of p53 via the Ub-proteasome pathway."
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No evidence text available
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Ubiquitinated TP53 binds ATXN3. 1 / 1
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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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TP53 binds ATXN3 and LFS. 1 / 1
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"LFS is associated with autosomal dominant mutations of TP53 (p53) resulting in an elevated incidence and early onset of a wide variety of cancers in multiple tissues (sarcoma, carcinoma and leukaemi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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ATXN3 activates TP53.
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ATXN3 activates TP53. 10 / 18
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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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"Using the zebrafish model system, we further examined whether ATX-3 induces p53 dependent apoptosis in vivo."
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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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"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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"As P53 has known functions in cycle arrest and apoptosis, this indicates that expression of atxn3 polyQ repeats induces selective transcription and expression of p53 target genes and promotes p53 dependent apoptosis in the CNS of zebrafish [XREF_BIBR]."
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"ATX-3 Promotes p53 Dependent Apoptosis in Cells and in Zebrafish."
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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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"The expression levels of p53 responsive genes (such as p21 and Puma) were also higher in ATX-3 exp (80Q) expressing RKO cells (XREF_SUPPLEMENTARY), suggesting that p53 was functionally enhanced by polyQ expansion in ATX-3."
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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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"Besides, we found that the degradation of p53 in the ATX-3 exp (80Q)-expressing cells was slower than that of normal ATX-3-expressing cells (XREF_SUPPLEMENTARY), and ectopic expression of polyQ expanded ATX-3 induced higher levels of p53 protein than the normal ATX-3 in RKO, 293T, and MEF cells (XREF_SUPPLEMENTARY), indicating that polyQ expanded ATX-3 possessed enhanced capability to stabilize p53."
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Mutated ATXN3 activates TP53. 6 / 6
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"Mutant ATXN3 activates the pro apoptotic p53 pathway by activating ATM 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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"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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"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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"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."
25590633
Modified ATXN3 activates TP53. 1 / 1
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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."
28959952
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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"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."
29867345
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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"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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"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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Modified ATXN3 increases the amount of TP53. 1 / 1
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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."
28959952
ATXN3 deubiquitinates TP53.
1 | 2
ATXN3 deubiquitinates TP53. 3 / 3
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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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"Review"
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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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ATXN3 ubiquitinates TP53.
| 1
Mutated ATXN3 leads to the ubiquitination of TP53. 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
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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 | 14 18
TP53 binds ATXN3.
5 | 12 18
TP53 binds ATXN3. 10 / 40
5 | 11 17
sparser
"Li-Fraumeni syndrome (LFS) is an autosomal dominant disease that is associated with germline TP53 mutations and it predisposes affected individuals to a high risk of developing multiple tumors."
30107858
reach
"We wonder whether the polyQ expansion affects the ATX-3 and p53 interaction."
27851749
reach
"We have found that ATX-3 interacts with p53 and functions as a novel p53 DUB."
27851749
sparser
"Therefore, both the Josephin and UIM domain coordinately regulate the interaction between ATX-3 and p53 ( xref )."
27851749
sparser
"The interaction between ATX-3 and p53 was confirmed under physiological condition ( xref ) and with in vitro purified forms ( xref ), indicating a direct association between these two proteins."
27851749
biogrid
No evidence text available
27851749
sparser
"Consistently, as shown in xref , the cysteine 14 mutation did not affect the binding of ATX-3 to either native or ubiquitinated p53, whereas the ΔN mutant lost its binding to both forms of p53."
27851749
sparser
"Instructively, mutations effecting the expression of p53 are associated with Li Fraumini syndrome, an autosomal dominant hereditary cancer predisoposition syndrome."
20346505
sparser
"As ATX-3 interacts with p53 under physiological conditions and regulates the ubiquitination of p53 in cells, it is possible that ATX-3 may regulate the turnover of p53 via the Ub-proteasome pathway."
27851749
biogrid
No evidence text available
27851749
Ubiquitinated TP53 binds ATXN3. 1 / 1
| 1
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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
TP53 binds ATXN3 and LFS. 1 / 1
| 1
sparser
"LFS is associated with autosomal dominant mutations of TP53 (p53) resulting in an elevated incidence and early onset of a wide variety of cancers in multiple tissues (sarcoma, carcinoma and leukaemi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
21802523
TP53 activates ATXN3.
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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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