p53: oncogene or anti-oncogene?

Lane, David P.; Benchimol, Samuel

doi:10.1101/gad.4.1.1

Cited by 761 publications

(309 citation statements)

References 52 publications

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“…Mostly, they are single missense point mutations located within the central region (amino acid residues 100-300 of the p53 protein ) and these mutant p53 proteins lose the tumor-suppresser function. 58 In the present study, a mutation of p53 in HCT8DDP cells was found in a transcriptional domain. SP1 -DNA binding activity was suppressed by the wild -type p53 in A2780 cells as it was by a mutant p53 in HCT8DDP cells, suggesting that the inhibitory activity of SP1 transcription seems to be same in these cancer cells with wild and mutant type p53 (Fig 9A ).…”

Section: Discussionsupporting

confidence: 47%

Hammerhead ribozyme against γ-glutamylcysteine synthetase sensitizes human colonic cancer cells to cisplatin by down-regulating both the glutathione synthesis and the expression of multidrug resistance proteins

et al. 2001

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Multidrug resistance in cancer cells is often associated with an elevation in the concentration of glutathione ( GSH ) and the expression of -glutamylcysteine synthetase ( -GCS ), a rate -limiting enzyme for GSH. We constructed a hammerhead ribozyme against a -GCS heavy subunit ( -GCSh ) mRNA transcript and transfected it to human colonic cancer cells ( HCT8DDP ) resistant to cisplatin ( CDDP ). The effect of the ribozyme transfection on the drug resistance of cancer cells was studied.

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Section: Discussionsupporting

confidence: 47%

Hammerhead ribozyme against γ-glutamylcysteine synthetase sensitizes human colonic cancer cells to cisplatin by down-regulating both the glutathione synthesis and the expression of multidrug resistance proteins

et al. 2001

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“…Initially associated with the regulation of cell proliferation (Reich and Levine 1984), the p53 molecule has been identified as the first known tumor suppressor that is inactivated in most human cancers (Lane and Benchimol 1990;Vogelstein et al 2000). In homeostatic cells, the level of p53 protein is downregulated via the binding of specific proteins that promote p53 degradation via the ubiquitin/proteasome pathway.…”

Section: P53mentioning

confidence: 99%

Obesity and related consequences to ageing

Jura

Kozak

2016

AGE

306

203

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Obesity has become a major public health problem. Given the current increase in life expectancy, the prevalence of obesity also raises steadily among older age groups. The increase in life expectancy is often accompanied with additional years of susceptibility to chronic ill health associated with obesity in the elderly. Both obesity and ageing are conditions leading to serious health problems and increased risk for disease and death. Ageing is associated with an increase in abdominal obesity, a major contributor to insulin resistance and the metabolic syndrome. Obesity in the elderly is thus a serious concern and comprehension of the key mechanisms of ageing and age-related diseases has become a necessary matter. Here, we aimed to identify similarities underlying mechanisms related to both obesity and ageing. We bring together evidence that age-related changes in body fat distribution and metabolism might be key factors of a vicious cycle that can accelerate the ageing process and onset of age-related diseases.

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“…In response to multiple stresses including DNA damage, oncogene activation and hypoxia, the tumour-suppressor p53 is stabilized and its activity is increased leading to cell cycle arrest or apoptosis (Lane and Benchimol, 1990;Vousden and Lu, 2002). p53 is repressed by Mdm2 and its homologue MdmX, which share high sequence similarity particularly in the p53-binding domain and the RING finger domains (Marine et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

MdmX is a substrate for the deubiquitinating enzyme USP2a

et al. 2009

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It has previously been shown that ubiquitin-specific protease 2a (USP2a) is a regulator of the Mdm2/p53 pathway. USP2a binds to Mdm2 and can deubiquitinate Mdm2 without reversing Mdm2-mediated p53 ubiquitination. Overexpression of USP2a causes accumulation of Mdm2 and promotes p53 degradation. We now show that MdmX is also a substrate for USP2a. MdmX associates with USP2a independently of Mdm2. Ectopic expression of wild-type USP2a but not a catalytic mutant prevents Mdm2-mediated degradation of MdmX. This correlates with the ability of wild-type USP2a to deubiquitinate MdmX. siRNA-mediated knockdown of USP2a in NTERA-2 testicular embryonal carcinoma cells and MCF7 breast cancer cells causes destabilization of MdmX and results in a decrease in MdmX protein levels, showing that endogenous USP2a participates in the regulation of MdmX stability. The therapeutic drug, cisplatin decreases MdmX protein expression. USP2a mRNA and protein levels were also reduced after cisplatin exposure. The magnitude and time course of USP2a downregulation suggests that the reduction in USP2a levels could contribute to the decrease in MdmX expression following treatment with cisplatin. Knockdown of USP2a increases the sensitivity of NTERA-2 cells to cisplatin, raising the possibility that suppression of USP2a in combination with cisplatin may be an approach for cancer therapy.

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p53: oncogene or anti-oncogene?

Cited by 761 publications

References 52 publications

Hammerhead ribozyme against γ-glutamylcysteine synthetase sensitizes human colonic cancer cells to cisplatin by down-regulating both the glutathione synthesis and the expression of multidrug resistance proteins

Hammerhead ribozyme against γ-glutamylcysteine synthetase sensitizes human colonic cancer cells to cisplatin by down-regulating both the glutathione synthesis and the expression of multidrug resistance proteins

Obesity and related consequences to ageing

MdmX is a substrate for the deubiquitinating enzyme USP2a

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