IndraLab

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Mutated TP53 activates TP53. 17 / 17
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"These results support the hypothesis that TP53 mutations play a role in the late stage of tumorigenesis, such as progression step of adenomas to invasive adenocarcinomas or metastasis to distant organs.Cellular stress, like DNA damage, telomere erosion, hypoxia, and nutrient depletion, as well as oncogenic signaling, activates p53, leading to the promotion of cell-cycle arrest, senescence, and apoptosis depending on the extent and context of the stress (Vousden and Lu, 2002; Vousden and Prives, 2009)."
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"In light of these observations, it is not surprising that the loss of p53 wild-type activity caused by most TP53 mutations results in a deregulated tumor cell secretome impacting on the reciprocal crosstalk of tumor cells with the plethora of cell types in their microenvironment."
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"Unlike wt p53, mutant p53 is normally expressed at high levels in tumor cells, most likely due to the inability to induce components of p53 negative-feedback loops such as MDM2, Cop1, or Pirh2."
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"These data indicate that ectopic expression of wild-type p53 can repress dUTPase promoter activity and that ectopic p53 mutant expression can induce dUTPase promoter activity in the HCT116 p53 isogenic cell-line models."
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"We show here that overexpression of the GOF mutant p53 G245D and other GOF p53 mutants enhances the invasive cell growth of p53 deficient head and neck squamous cell carcinoma (HNSCC) UM-SCC-1 cells both in in vitro three-dimensional culture and in an in vivo orthotopic nude mouse model of HNSCC through a novel transcription independent mechanism."
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"This suggests that acetylation at K320 and K373 can alter the structure of mutant p53 and restore wild type p53 functions."
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"TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer."
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"Over-expression of the dominant negative p53 mutant DeltaTAp53, which inhibits p53 activity, prevented the TPA induced K14 down-regulation in C9 cells."
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"A p53 mutant protein fails to transcribe the MDM-2 gene and in the absence of an MDM-2 protein the mutant p53 protein levels increase up to ten fold more p53 protein compared to cells with wild type p53."
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"These ' gain-of-function ' (GOF) TP53 mutations cause mutp53 to accumulate at high levels in cells, contributing to tumorigenesis and the development of drug resistance XREF_BIBR."
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"The overexpression of mutant p53 stimulates serum p53 antibody production in patients with colorectal carcinoma even in superficial tumors."
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"EZH2 augmented p53 GOF mutant mediated cancer growth and metastasis by increasing protein levels of mutant p53."
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"P53 tumor suppressor protein is involved in the regulation of centrosome duplication : loss of p53 as well as expression of certain p53 mutants result in deregulated centrosome duplication and centrosome amplification."
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"The first such mechanism discovered showed that mutant p53 proteins abrogate the tumor-suppressive activities of the p53 family members p63 and p73."
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"More significantly, Ser20 phosphorylation of specific p53 mutants with oxali-Pt also activates p53 function, and this raises the likelihood that other p53 mutants in refractory human ovarian cancers could also be functionally activated with distinct drugs, such as oxali-Pt, to restore therapeutic sensitivity."
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"Somewhat surprisingly, we found that expression of a dominant negative TP53 mutant that inactivates TP53 by forming non functional tetramers (Gottlieb et al., 1994), decreased rather than increased CC[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"As expected, mutant p53 expressed in SKNBe2C and SKNAS cells remained unaffected by MDM2-p53 antagonist treatment, but induced p53 stabilisation in p53 wt SHSY5Y cells (XREF_FIG)."
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