IndraLab

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TP53 activates mutated TP53. 29 / 29
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"Previously, our lab discovered that metastatic ascites cells (28–2) from our orthotopic, syngeneic murine model of ovarian cancer were p53 mutant, compared to p53 wild-type ID8 cells used for tumor induction [6], suggesting interaction with the ovarian microenvironment initiated the development of a TP53 mutation."
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"Genotoxic stressors cause strong promoter activation and upregulation of p53 transcription, which could increase p53 mutation frequencies."
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"It is noteworthy that in all of these cancers, heterogeneity of TP53 expression could be observed, raising the possibility of focal TP53 mutations in a tumour subclone that may not have been detected by the sequencing assays."
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"The constitutive overexpression of p53 overcame endogenous negative regulation in D283 cells, and rescued TP53 mutation in VP-16-treated Daoy cells."
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"Although P53 is typically considered a “tumor suppressor” protein that binds to and repairs damaged DNA or signals for apoptosis in irreparable cells, missense mutations in TP53 elicit mutant p53 proteins with potential gain-of-function properties that stimulate tumor cell proliferation, migration, invasion, survival, chemoresistance, cancer metabolism and/or tissue architecture disruption [65]."
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"Sirt1 may inactivate the 382nd lysine residue of p53, reduce the expression of the wild-type p53 protein combining with the DNA cis element to promote p53 mutation."
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"19 In this paper, we report that Delta122p53 enhanced the tumor-suppressor activities of the attenuated p53 mutant mDeltapro."
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"Mutations in TP53 diminish its anticancer activity and enhance the oncogenic properties of the mutant p53 protein (62)."
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"This statement could be supported by previous studies showing that S15 phosphorylation of TP53 contributed mutant TP53 stability, thereby prolonging cell viability in ovarian cancer cells, and S392 phosphorylation in mutant TP53 could lead to tumor progression in esophageal squamous cell carcinoma."
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"Second, the false positive rate of p53 protein expression in healthy subjects is ~5%, which may cause the p53 protein partially reflect the tumor's TP53 mutation (Luo et al., 1995)."
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"ESR1 mutant tumors do not exhibit differential p53 pathway activity, whereas we identified attenuated ER activity and expression in TP53 mutant tumors, driven by a p53-associated E2 response gene signature."
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"11 , 12 , 13 TP53 GOF mutations produce mutant p53 proteins with oncogenic functions, which are independent of wild‐type (WT) p53 functions."
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"As coexpression of wild-type p53 protein was shown to promote destabilization of the mutant p53 protein [15], the above difference supports the idea that the tumors retaining heterozygosity at the sit[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"While we found a strong repression of p53 signaling activity in TP53 mutant tumors in TCGA as a reference (Supplementary Fig. 2a), ESR1 mutations did not change the p53 signatures (Fig. 2d)."
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"In the absence of stress, p53 is stochastically expressed, activating nuclear Akt in an on/off mode, whereas mutant p53 is highly expressed and activates nuclear Akt constitutively, reflecting the hyperstability of mutant p53 relative to p53 ."
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"XREF_BIBR The targeting of mutant TP53 epitopes or TP53 overexpression in tumors by vaccine has shown promise in a number of in vivo settings."
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"On the other hand, overexpressed RPS27 may in turn stabilize mutant p53, since ectopic expression of RPS27 could increase p53 levels (XREF_FIG)."
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"Of note, in all of these cases, heterogeneity of p53 expression could be observed, raising the possibility of focal TP53 mutations in a tumor subclone that may not have been detected by the sequencing assays (XREF_FIG)."
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"However, a complete absence of p53 expression in RP specimens, after careful review in cases with higher grade (GG4, GG5) lesions, may raise the possibility of a null TP53 mutation (frameshift, truncating mutations)."
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"Here, we characterize protumorigenic consequences of WT TP53 LOH in LFS cells and report that these consequences can be abolished by pCAP-mediated mutant p53 reactivation, suggesting that pCAPs may be considered for cancer prevention in LFS mutation carriers."
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"In addition to the loss of wild-type p53 function, TP53 LOH causes nuclear stabilization of mutant p53, which is required for its oncogenic role of mutant p53."
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"We found that JNK mediated phosphorylation of Thr 81 in the proline rich domain (PRD) of p53 enabled wild-type p53, as well as mutant p53, to form a complex with p73."
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"P53 protein content is determined using immunohistochemistry, and increased p53 expression is assumed to be due to overexpression of mutant p53."
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"Thus, these data indicate that GCS suppression restores wild-type p53 expression and leads mutant p53 tumors to induced-apoptosis."
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"The key role of p53 in mediating cell-cycle arrest or programmed cell death in response to intrinsic stress signals associated with tumorigenesis, including unscheduled DNA replication, telomere erosi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Low p53 RNA levels in both the human and the mouse cell lines suggested that mis-splicing drives nonsense-mediated decay of the mutant p53 mRNA.Our findings in the human samples are consistent with previous studies that did not observe detectable p53 protein in the NCI-H716 cell line as well as experiments that used available human data and in-vitro assays to investigate alternative splicing at this site [42–45]."
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"TP53, encoding the tumor suppressor p53, is frequently mutated in various cancers, producing mutant p53 proteins (mutp53) which can exhibit neomorphic, gain-of-function properties."
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"Delta122p53, a mouse model of Delta133p53alpha, enhances the tumor-suppressor activities of an attenuated p53 mutant."
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"The p53 levels in cyclin D1-HA and FHL2 -/- cells were as high as those in wt MEFs in the absence of treatment, and did not increase in response to doxo, reflecting mutant p53 (XREF_FIG), and similar results were obtained with two independent cyclin D1-HA and FHL2 -/- cell pools (data not shown)."
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