scholarly journals Gain-of-function mutant p53 downregulates miR-223 contributing to chemoresistance of cultured tumor cells

Oncogene ◽  
2013 ◽  
Vol 33 (12) ◽  
pp. 1601-1608 ◽  
Author(s):  
S Masciarelli ◽  
G Fontemaggi ◽  
S Di Agostino ◽  
S Donzelli ◽  
E Carcarino ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Mutant P53 ◽  
Gain Of Function ◽  
Cultured Tumor Cells

scholarly journals Mutant p53 Sequestration of the MDM2 Acidic Domain Inhibits E3 Ligase Activity

2018 ◽  
Vol 39 (4) ◽  
Author(s):  
Leixiang Yang ◽  
Tanjing Song ◽  
Qian Cheng ◽  
Lihong Chen ◽  
Jiandong Chen
Keyword(s):  
Tumor Cells ◽  
Recent Work ◽  
Intramolecular Interaction ◽  
E3 Ligase ◽  
Mutant P53 ◽  
Wild Type ◽  
Gain Of Function ◽  
Core Domain ◽  
Acidic Domain ◽  
Wild Type P53

ABSTRACT Missense p53 mutants often accumulate in tumors and drive progression through gain of function. MDM2 efficiently degrades wild-type p53 but fails to degrade mutant p53 in tumor cells. Previous studies revealed that mutant p53 inhibits MDM2 autoubiquitination, suggesting that the interaction inhibits MDM2 E3 activity. Recent work showed that MDM2 E3 activity is stimulated by intramolecular interaction between the RING and acidic domains. Here, we show that in the mutant p53-MDM2 complex, the mutant p53 core domain binds to the MDM2 acidic domain with significantly higher avidity than wild-type p53. The mutant p53-MDM2 complex is deficient in catalyzing ubiquitin release from the activated E2 conjugating enzyme. An MDM2 construct with extra copies of the acidic domain is resistant to inhibition by mutant p53 and efficiently promotes mutant p53 ubiquitination and degradation. The results suggest that mutant p53 interferes with the intramolecular autoactivation mechanism of MDM2, contributing to reduced ubiquitination and increased accumulation in tumor cells.

scholarly journals Semi-Synthesis of Small Molecules of Aminocarbazoles: Tumor Growth Inhibition and Potential Impact on p53

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1637
Author(s):  
Solida Long ◽  
Joana B. Loureiro ◽  
Carla Carvalho ◽  
Luís Gales ◽  
Lucília Saraiva ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Small Molecules ◽  
Tumor Cells ◽  
Mutant P53 ◽  
Wild Type ◽  
Naturally Occurring ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Amino Derivatives ◽  
Carbazole Alkaloids

The tumor suppressor p53 is inactivated by mutation in approximately 50% of human cancers. Small molecules that bind and stabilize those mutants may represent effective anticancer drugs. Herein, we report the tumor cell growth inhibitory activity of carbazole alkaloids and amino derivatives, as well as their potential activation of p53. Twelve aminocarbazole alkaloids were semi-synthesized from heptaphylline (1), 7-methoxy heptaphylline (2), and 7-methoxymukonal (3), isolated from Clausena harmandiana, using a reductive amination protocol. Naturally-occurring carbazoles 1–3 and their amino derivatives were evaluated for their potential effect on wild-type and mutant p53 activity using a yeast screening assay and on human tumor cell lines. Naturally-occurring carbazoles 1–3 showed the most potent growth inhibitory effects on wild-type p53-expressing cells, being heptaphylline (1) the most promising in all the investigated cell lines. However, compound 1 also showed growth inhibition against non-tumor cells. Conversely, semi-synthetic aminocarbazole 1d showed an interesting growth inhibitory activity in tumor cells expressing both wild-type and mutant p53, exhibiting low growth inhibition on non-tumor cells. The yeast assay showed a potential reactivation of mutant p53 by heptaphylline derivatives, including compound 1d. The results obtained indicate that carbazole alkaloids may represent a promising starting point to search for new mutp53-reactivating agents with promising applications in cancer therapy.

Effects of mistletoe (Viscum album L.) extracts on cultured tumor cells

1987 ◽  
Vol 19 (3) ◽  
pp. 337
Author(s):  
G Ribereau-Gayon ◽  
ML Jung ◽  
S Baudino
Keyword(s):  
Tumor Cells ◽  
Viscum Album ◽  
Cultured Tumor Cells

Antibodies to Cultured Tumor Cells Detected in Sera of Renal Cell Carcinoma Patients by a Quantitative Avidin-Biotin Method

1986 ◽  
Vol 136 (4) ◽  
pp. 795-798
Author(s):  
Jean B. deKernion ◽  
Laszlo Lovrekovich ◽  
Dominique Chopin ◽  
Urs E. Studer
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Renal Cell ◽  
Cultured Tumor Cells

New allelic variant of triosephosphate isomerase found in cultured tumor cells of human prostate

2011 ◽  
Vol 26 (1) ◽  
pp. 14-20
Author(s):  
L. I. Kovalev ◽  
A. A. Makarov ◽  
E. A. Cherkashin ◽  
J. Dulinska ◽  
M. A. Kovaleva ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Triosephosphate Isomerase ◽  
Allelic Variant ◽  
Human Prostate ◽  
Cultured Tumor Cells

scholarly journals Pontin, a novel interactor of mutant p53 that promotes mutant p53 gain of function

2015 ◽  
Vol 3 (2) ◽  
pp. e1076587
Author(s):  
Yuhan Zhao ◽  
Xuetian Yue ◽  
Wenwei Hu
Keyword(s):  
Mutant P53 ◽  
Gain Of Function
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