scholarly journals Novel phosphorylation sites of human tumour suppressor protein p53 at Ser20 and Thr18 that disrupt the binding of mdm2 (mouse double minute 2) protein are modified in human cancers

1999 ◽  
Vol 342 (1) ◽  
pp. 133 ◽  
Author(s):  
Ashley L. CRAIG ◽  
Lindsay BURCH ◽  
Borek VOJTESEK ◽  
Jaroslava MIKUTOWSKA ◽  
Alastair THOMPSON ◽  
...  
Keyword(s):  
Tumour Suppressor ◽  
Phosphorylation Sites ◽  
Human Tumour ◽  
Human Cancers ◽  
Mouse Double Minute ◽  
Protein P53 ◽  
Tumour Suppressor Protein ◽  
Double Minute

scholarly journals Novel phosphorylation sites of human tumour suppressor protein p53 at Ser20 and Thr18 that disrupt the binding of mdm2 (mouse double minute 2) protein are modified in human cancers

1999 ◽  
Vol 342 (1) ◽  
pp. 133-141 ◽  
Author(s):  
Ashley L. CRAIG ◽  
Lindsay BURCH ◽  
Borek VOJTESEK ◽  
Jaroslava MIKUTOWSKA ◽  
Alastair THOMPSON ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Insect Cells ◽  
Phosphorylation Site ◽  
Tumour Suppressor ◽  
Phosphorylation Sites ◽  
Human Tumour ◽  
Human Cancers ◽  
Mouse Double Minute ◽  
Tumour Suppressor Protein ◽  
Double Minute

The ability to separate the isoforms of human tumour suppressor protein p53 expressed in insect cells using heparin-Sepharose correlates with differences in the isoelectric point of p53, demonstrating that p53 can be heterogeneously modified and providing support for the use of insect cells as a model system for identifying novel signalling pathways that target p53. One p53 isoform that was reduced in its binding to the monoclonal antibody DO-1 could be stimulated in its binding to DO-1 by prior incubation with protein phosphatases, suggesting the presence of a previously unidentified N-terminal phosphorylation site capable of masking the DO-1 epitope. A synthetic peptide from the N-terminal domain of p53 containing phosphate at Ser20 inhibited DO-1 binding, thus identifying the phosphorylation site responsible for DO-1 epitope masking. Monoclonal antibodies overlapping the DO-1 epitope were developed that are specific for phospho-Thr18 (adjacent to the DO-1 epitope) and phospho-Ser20 (within the DO-1 epitope) to determine whether direct evidence could be obtained for novel phosphorylation sites in human p53. A monoclonal antibody highly specific for phospho-Ser20 detected significant phosphorylation of human p53 expressed in insect cells, whereas the relative proportion of p53 modified at Thr18 was substantially lower. The relevance of these two novel phosphorylation sites to p53 regulation in human cells was made evident by the extensive phosphorylation of human p53 at Thr18 and Ser20 in a panel of human breast cancers with a wild-type p53 status. Phospho-Ser20 or phospho-Thr18 containing p53 peptides are as effective as the phospho-Ser15 peptide at reducing mdm2 (mouse double minute 2) protein binding, indicating that the functional effects of these phosphorylation events might be to regulate the binding of heterologous proteins to p53. These results provide evidence in vivo for two novel phosphorylation sites within p53 at Ser20 and Thr18 that can affect p53 protein-protein interactions and indicate that some human cancers might have amplified one or more Ser20 and Thr18 kinase signalling cascades to modulate p53 activity.

scholarly journals Tumour suppressor protein p53 regulates the stress activated bilirubin oxidase cytochrome P450 2A6

2015 ◽  
Vol 289 (1) ◽  
pp. 30-39 ◽  
Author(s):  
Hao Hu ◽  
Ting Yu ◽  
Satu Arpiainen ◽  
Matti A. Lang ◽  
Jukka Hakkola ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Tumour Suppressor ◽  
Bilirubin Oxidase ◽  
Protein P53 ◽  
Tumour Suppressor Protein ◽  
Cytochrome P450 2A6

scholarly journals The Establishment of a Hyperactive Structure Allows the Tumour Suppressor Protein p53 to Function through P-TEFb during Limited CDK9 Kinase Inhibition

PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0146648 ◽  
Author(s):  
Thomas K. Albert ◽  
Claudia Antrecht ◽  
Elisabeth Kremmer ◽  
Michael Meisterernst
Keyword(s):  
Tumour Suppressor ◽  
Kinase Inhibition ◽  
Protein P53 ◽  
Tumour Suppressor Protein

scholarly journals Cancer and Tumour Suppressor p53 Encounters at the Juncture of Sex Disparity

2021 ◽  
Vol 12 ◽  
Author(s):  
Sue Haupt ◽  
Ygal Haupt
Keyword(s):  
Tumour Suppressor ◽  
Redox Activity ◽  
Epigenetic Alterations ◽  
Chief Operating Officer ◽  
Protein P53 ◽  
Tumour Suppressor Protein ◽  
Sex Disparities ◽  
Males And Females ◽  
Sex Disparity ◽  
Tumour Suppressor P53

There are many differences in cancer manifestation between men and women. New understanding of the origin of these point to fundamental distinctions in the genetic code and its demise. Tumour suppressor protein p53 is the chief operating officer of cancer defence and critically acts to safeguard against sustained DNA damaged. P53 cannot be ignored in cancer sex disparity. In this review we discuss the greater prevalence and associated death rates for non-reproductive cancers in males. The major tumour suppressor protein p53, encoded in the TP53 gene is our chosen context. It is fitting to ask why somatic TP53 mutation incidence is estimated to be disproportionately higher among males in the population for these types of cancers compared with females? We scrutinised the literature for evidence of predisposing genetic and epigenetic alterations that may explain this sex bias. Our second approach was to explore whether redox activity, either externally imposed or inherent to males and females, may define distinct risks that could contribute to the clear cancer sex disparities.

Tumour suppressor protein p53 released by nuclease digestion increases at the onset of rat liver regeneration

1999 ◽  
Vol 31 (2) ◽  
pp. 306-314 ◽  
Author(s):  
Francesc Miró ◽  
Jean-Claude Lelong ◽  
Floria Pancetti ◽  
Nerea Roher ◽  
Arlette Duthu ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Rat Liver ◽  
Tumour Suppressor ◽  
Rat Liver Regeneration ◽  
Protein P53 ◽  
Tumour Suppressor Protein ◽  
Nuclease Digestion

Redox regulation of tumour suppressor protein p53: identification of the sites of hydrogen peroxide oxidation and glutathionylation

2013 ◽  
Vol 4 (3) ◽  
pp. 1257 ◽  
Author(s):  
Jenna Scotcher ◽  
David J. Clarke ◽  
C. Logan Mackay ◽  
Ted Hupp ◽  
Peter J. Sadler ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Redox Regulation ◽  
Tumour Suppressor ◽  
Peroxide Oxidation ◽  
Protein P53 ◽  
Tumour Suppressor Protein ◽  
Hydrogen Peroxide Oxidation

scholarly journals Expression profile of tumour suppressor protein p53 and its regulator MDM2 in a cohort of breast cancer patients in a Tertiary Hospital in Ghana

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258543
Author(s):  
Francis Opoku ◽  
Kweku Bedu-Addo ◽  
Nicholas Akinwale Titiloye ◽  
Elijah Atta Manu ◽  
Charity Ameh-Mensah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Histological Grade ◽  
Phenotypic Expression ◽  
Tumour Suppressor ◽  
P53 Expression ◽  
Protein P53 ◽  
Tumour Suppressor Protein ◽  
Mdm2 Expression

Background Inactivation or mutation of the tumour suppressor gene p53 or its regulator mouse double minute 2 (MDM2) is the commonest event in breast cancer. These altered genes usually express abnormally high levels of their proteins in many carcinomas. The phenotypic expression of p53 and MDM2 in breast cancer cases in our setting is not known. This study investigated the expression of the tumour suppressor protein p53 and its regulator MDM2, using immunohistochemistry in a Ghana breast cancer cohort. Method A 9-year retrospective cross-sectional study on archived tissue blocks–formalin fixed paraffin embedded tissue (FFPE) was carried out. Demographic data were abstracted. Based on complete clinical data and availability of FFPE archived blocks 203 cases were selected for tissue micro array (TMA) construction. The TMA sections were subjected to immunohistochemistry (IHC) (ER, PR, HER2, p53, and MDM2). Expression of p53 and MDM2 were related to grade and molecular subtypes. Results The age ranged from 17 to 92 years (mean = 49.34 ± 13.74). Most of the cases were high grade; grade II (34.9%) and grade III (55.7%). Fifty-four percent of the cases were triple negative. Invasive ductal carcinoma no special type was the commonest histotype (87.1%). Thirty-six percent (36%) of the cases expressed p53. Significant associations were found between p53 overexpression and histological grade (p = 0.034), triple negative (p = 0.0333) and luminal B (p<0.01) tumors. Most cases (93.1%) were negative for MDM2 expression. Significant association was found between MDM2 and HER2 over-expression as well as Ki-67. There was no significant positive correlation between MDM2 and p53 co-expression (p>0.05). Conclusion The elevated level of p53 expression in the aggressive breast cancer phenotypes (high histological grade and triple negative) in our cohort suggest that P53 elevation may be a poor prognostic marker in our setting. High expression of MDM2 in our cohort with high Ki67; also in cases with Her2/neu overexpression known with predictable poor prognosis in the absence of target therapy suggest MDM2 may be associated with aggressive biological behaviour in our breast cancer cases. The non-significant association of p53 and MDM2 expression in the same cases as also documented by previous studies suggest independent genetic pathway in tumourigenesis.

Sites in human nuclei where damage induced by ultraviolet light is repaired: localization relative to transcription sites and concentrations of proliferating cell nuclear antigen and the tumour suppressor protein, p53

1994 ◽  
Vol 107 (7) ◽  
pp. 1753-1760 ◽  
Author(s):  
D.A. Jackson ◽  
A.B. Hassan ◽  
R.J. Errington ◽  
P.R. Cook
Keyword(s):  
Ultraviolet Light ◽  
Proliferating Cell Nuclear Antigen ◽  
Active Sites ◽  
Tumour Suppressor ◽  
Nuclear Antigen ◽  
High Concentration ◽  
Repair Synthesis ◽  
Protein P53 ◽  
Tumour Suppressor Protein ◽  
Proliferating Cell

The repair of damage induced in DNA by ultraviolet light involves excision of the damaged sequence and synthesis of new DNA to repair the gap. Sites of such repair synthesis were visualized by incubating permeabilized HeLa or MRC-5 cells with the DNA precursor, biotin-dUTP, in a physiological buffer; then incorporated biotin was immunolabeled with fluorescent antibodies. Repair did not take place at sites that reflected the DNA distribution; rather, sites were focally concentrated in a complex pattern. This pattern changed with time; initially intense repair took place at transcriptionally active sites but when transcription became inhibited it continued at sites with little transcription. Repair synthesis in vitro also occurred in the absence of transcription. Repair sites generally contained a high concentration of proliferating cell nuclear antigen but not the tumour-suppressor protein, p53.

Sign in / Sign up

Export Citation Format

Share Document