Nitric Oxide Nitrates Tyrosine Residues of Tumor-Suppressor p53 Protein in MCF-7 Cells

p53 is an important tumor suppressor, normally preventing cancer development via apoptosis. A genomic Arg72Pro substitution in the p53 protein has important influence on cell death via apoptosis, which could be beneficial. We therefore tested the hypotheses that this polymorphism influences longevity, survival after a cancer diagnosis, and risk of cancer in the general population. We examined a cohort of 9,219 participants ages 20–95 from the Danish general population with 100% follow-up. The overall 12-yr survival was increased in p53 Arg/Pro heterozygotes with 3% (P = 0.003) and in Pro/Pro homozygotes with 6% (P = 0.002) versus Arg/Arg homozygotes, corresponding to an increase in median survival of 3 yr for Pro/Pro versus Arg/Arg homozygotes. We also demonstrated an increased survival after the development of cancer, or even after the development of other life-threatening diseases, for Pro/Pro versus Arg/Arg homozygotes. The Arg72Pro substitution did not associate with decreased risk of cancer. In conclusion, in this large cohort from the general population, we show that a well-known functional single nucleotide polymorphism in the tumor suppressor p53 protein leads to increased longevity, but not to decreased risk of cancer. The increased longevity may be due to increased survival after a diagnosis of cancer or other life-threatening diseases.

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Expression of the Antiapoptotic Protein bcl-2 Is Not Dependent on the Tumor Suppressor p53 Protein in Indian Breast Carcinoma

Pathobiology ◽

10.1159/000164111 ◽

1997 ◽

Vol 65 (2) ◽

pp. 108-112 ◽

Cited By ~ 6

Author(s):

Lakshmi Kesari ◽

V.G. Chellam ◽

Jayaprakash Madhavan ◽

P.P. Nair ◽

Krishnan Nair ◽

...

Keyword(s):

Breast Carcinoma ◽

Tumor Suppressor ◽

P53 Protein ◽

Tumor Suppressor P53 ◽

Antiapoptotic Protein

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Toward Cancer Diagnostics of the Tumor Suppressor p53 by Surface Enhanced Raman Spectroscopy

Sensors ◽

10.3390/s20247153 ◽

2020 ◽

Vol 20 (24) ◽

pp. 7153

Author(s):

Anna Rita Bizzarri ◽

Salvatore Cannistraro

Keyword(s):

Raman Spectroscopy ◽

Tumor Suppressor ◽

P53 Protein ◽

Surface Enhanced Raman Spectroscopy ◽

Cancer Diagnostics ◽

Clinical Diagnostics ◽

Tumor Suppressor P53 ◽

Wild Type ◽

Surface Enhanced ◽

Surface Enhanced Raman

The tumor suppressor p53 protein plays a crucial role in many biological processes. The presence of abnormal concentrations of wild-type p53, or some of its mutants, can be indicative of a pathological cancer state. p53 represents therefore a valuable biomarker for tumor screening approaches and development of suitable biosensors for its detection deserves a high interest in early diagnostics. Here, we revisit our experimental approaches, combining Surface Enhanced Raman Spectroscopy (SERS) and nanotechnological materials, for ultrasensitive detection of wild-type and mutated p53, in the perspective to develop biosensors to be used in clinical diagnostics. The Raman marker is provided by a small molecule (4-ATP) acting as a bridge between gold nanoparticles (NPs) and a protein biomolecule. The Azurin copper protein and specific antibodies of p53 were used as a capture element for p53 (wild-type and its mutants). The developed approaches allowed us to reach a detection level of p53 down to 10−17 M in both buffer and serum. The implementation of the method in a biosensor device, together with some possible developments are discussed.

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Runt-related Transcription Factor 1 (RUNX1) Stimulates Tumor Suppressor p53 Protein in Response to DNA Damage through Complex Formation and Acetylation

Journal of Biological Chemistry ◽

10.1074/jbc.m112.402594 ◽

2012 ◽

Vol 288 (2) ◽

pp. 1353-1364 ◽

Cited By ~ 28

Author(s):

Dan Wu ◽

Toshinori Ozaki ◽

Yukari Yoshihara ◽

Natsumi Kubo ◽

Akira Nakagawara

Keyword(s):

Dna Damage ◽

Transcription Factor ◽

Tumor Suppressor ◽

Complex Formation ◽

P53 Protein ◽

Tumor Suppressor P53 ◽

Related Transcription Factor ◽

Transcription Factor 1

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The double-stranded RNA activated protein kinase PKR physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro

Oncogene ◽

10.1038/sj.onc.1202620 ◽

1999 ◽

Vol 18 (17) ◽

pp. 2690-2702 ◽

Cited By ~ 130

Author(s):

Andrew R Cuddihy ◽

Andrew Hoi-Tao Wong ◽

Nancy Wai Ning Tam ◽

Suiyang Li ◽

Antonis E Koromilas

Keyword(s):

Protein Kinase ◽

Tumor Suppressor ◽

P53 Protein ◽

Tumor Suppressor P53 ◽

Double Stranded Rna ◽

Serine 392

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BAG2 promotes tumorigenesis through enhancing mutant p53 protein levels and function

eLife ◽

10.7554/elife.08401 ◽

2015 ◽

Vol 4 ◽

Cited By ~ 28

Author(s):

Xuetian Yue ◽

Yuhan Zhao ◽

Juan Liu ◽

Cen Zhang ◽

Haiyang Yu ◽

...

Keyword(s):

Tumor Suppressor ◽

Tumor Growth ◽

Poor Prognosis ◽

P53 Protein ◽

Underlying Mechanism ◽

Mutant P53 ◽

Tumor Suppressor P53 ◽

Protein Levels ◽

And Function

Tumor suppressor p53 is the most frequently mutated gene in tumors. Many mutant p53 (mutp53) proteins promote tumorigenesis through the gain-of-function (GOF) mechanism. Mutp53 proteins often accumulate to high levels in tumors, which is critical for mutp53 GOF. Its underlying mechanism is poorly understood. Here, we found that BAG2, a protein of Bcl-2 associated athanogene (BAG) family, promotes mutp53 accumulation and GOF in tumors. Mechanistically, BAG2 binds to mutp53 and translocates to the nucleus to inhibit the MDM2-mutp53 interaction, and MDM2-mediated ubiquitination and degradation of mutp53. Thus, BAG2 promotes mutp53 accumulation and GOF in tumor growth, metastasis and chemoresistance. BAG2 is frequently overexpressed in tumors. BAG2 overexpression is associated with poor prognosis in patients and mutp53 accumulation in tumors. These findings revealed a novel and important mechanism for mutp53 accumulation and GOF in tumors, and also uncovered an important role of BAG2 in tumorigenesis through promoting mutp53 accumulation and GOF.

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