Telomerase Activity and p53 Protein Accumulation in Lugol-Stained and Lugol-Unstained Esophageal Squamous Epithelia

2002 ◽  
pp. 201-208
Author(s):  
Yutaka Shimada ◽  
Maki Inai ◽  
Masato Kano ◽  
Takaki Sakurai ◽  
Tsutomu Chiba ◽  
...  
Keyword(s):  
P53 Protein ◽  
Telomerase Activity ◽  
Protein Accumulation ◽  
Squamous Epithelia

scholarly journals Chronology of p53 protein accumulation in gastric carcinogenesis.

Gut ◽  
1995 ◽  
Vol 36 (6) ◽  
pp. 848-852 ◽  
Author(s):  
M E Craanen ◽  
P Blok ◽  
W Dekker ◽  
G J Offerhaus ◽  
G N Tytgat
Keyword(s):  
P53 Protein ◽  
Gastric Carcinogenesis ◽  
Protein Accumulation

scholarly journals Myc and Human Papillomavirus Type 16 E7 Genes Cooperate To Immortalize Human Keratinocytes

2007 ◽  
Vol 81 (22) ◽  
pp. 12689-12695 ◽  
Author(s):  
Xuefeng Liu ◽  
Gary L. Disbrow ◽  
Hang Yuan ◽  
Vjekoslav Tomaić ◽  
Richard Schlegel
Keyword(s):  
Transcriptional Activation ◽  
High Efficiency ◽  
P53 Protein ◽  
Significant Proportion ◽  
Telomerase Activity ◽  
Human Papillomaviruses ◽  
Mrna Levels ◽  
Crisis Period ◽  
Cell Immortalization ◽  
Immortalized Cells

ABSTRACT The E6 protein of the oncogenic human papillomaviruses (HPVs), in combination with the E7 protein, is essential for the efficient immortalization of human foreskin keratinocytes (HFKs). Since we recently demonstrated that E6 activates the human telomerase reverse transcriptase (hTERT) promoter via a Myc-dependent mechanism, we speculated that overexpressed Myc might be able to substitute for E6 in cell immortalization. Myc (similar to E6) was unable to immortalize HFKs when transduced alone, despite inducing high levels of telomerase activity. However, when transduced with E7, Myc immortalized HFKs following a brief but detectable crisis period. In contrast to E6 + E7-immortalized cells, the Myc + E7-immortalized cells expressed high levels of p53 protein as well as two p53-regulated proteins, p21 and hdm-2. The increase in p21 and hdm-2 proteins correlated directly with their mRNA levels, suggesting transcriptional activation of the respective genes by the overexpressed p53 protein. Interestingly, a significant proportion of the p53 protein in the Myc + E7-immortalized cells was localized to the cytoplasm, potentially due to interactions with the overexpressed hdm-2 protein. Regardless, cell immortalization by the Myc + E7 genes occurred independently of p53 degradation. Since we have already observed high-efficiency cell immortalization with the hTERT + E7 or E6 mutant (p53 degradation-defective) + E7 genes (i.e., no crisis period) that proceeds in the presence of high levels of p53, we hypothesize that the crisis period in the Myc + E7 cells is due not to the levels of the p53 protein but rather to unique properties of the Myc protein. The common factor in cell immortalization by the three gene sets (E6 + E7, Myc + E7, and hTERT + E7 genes) is the induction of telomerase activity.

scholarly journals Amyloid-ß promotes neurotoxicity by Cdk5-induced p53 stabilization

2018 ◽  
Author(s):  
Rebeca Lapresa ◽  
Jesús Agulla ◽  
Irene Sánchez-Morán ◽  
Juan P. Bolaños ◽  
Angeles Almeida
Keyword(s):  
Neuronal Apoptosis ◽  
Therapeutic Strategy ◽  
Neuronal Damage ◽  
P53 Protein ◽  
Protein A ◽  
Tumor Suppressor Protein ◽  
Protein Accumulation ◽  
Brain Areas ◽  
P53 Tumor Suppressor Protein

ABSTRACTThe p53 tumor suppressor protein, a key regulator of cell apoptosis, has been described to accumulate in affected brain areas from Alzheimer’s disease (AD) patients. However, whether p53 plays any role in AD pathogenesis remains unknown. Here, we found that exposure of neurons to oligomers of the amyloidogenic fragment 25-35 of the Aß peptide (Aβ25-35) activated Cdk5, which promoted p53 protein phosphorylation and stabilization. Moreover, Aβ25-35-mediated mitochondrial dysfunction and neuronal apoptosis were prevented by both genetic and pharmacological inhibition of either p53 or Cdk5 activities. To confirm this mechanism in vivo, Aβ25-35 was stereotaxically injected in the cerebral right ventricle of mice, a treatment that caused p53 protein accumulation, dendrite disruption and neuronal death. Furthermore, these effects were prevented in p53 knockout mice or by pharmacologically inhibiting p53. Thus, Aβ25-35 triggers Cdk5 activation to induce p53 phosphorylation and stabilization, which leads to neuronal damage. Inhibition of the Cdk5-p53 pathway may therefore represent a novel therapeutic strategy against Aβ-induced neurodegeneration.

scholarly journals Regulation of p53 by Hypoxia: Dissociation of Transcriptional Repression and Apoptosis from p53-Dependent Transactivation

2001 ◽  
Vol 21 (4) ◽  
pp. 1297-1310 ◽  
Author(s):  
Constantinos Koumenis ◽  
Rodolfo Alarcon ◽  
Ester Hammond ◽  
Patrick Sutphin ◽  
William Hoffman ◽  
...  
Keyword(s):  
Dna Damage ◽  
Transcriptional Repression ◽  
Histone Deacetylases ◽  
Target Genes ◽  
P53 Protein ◽  
Genotoxic Stress ◽  
Protein Accumulation ◽  
Dependent Cell ◽  
Apoptotic Activity ◽  
Induced Apoptosis

ABSTRACT Hypoxic stress, like DNA damage, induces p53 protein accumulation and p53-dependent apoptosis in oncogenically transformed cells. Unlike DNA damage, hypoxia does not induce p53-dependent cell cycle arrest, suggesting that p53 activity is differentially regulated by these two stresses. Here we report that hypoxia induces p53 protein accumulation, but in contrast to DNA damage, hypoxia fails to induce endogenous downstream p53 effector mRNAs and proteins. Hypoxia does not inhibit the induction of p53 target genes by ionizing radiation, indicating that p53-dependent transactivation requires a DNA damage-inducible signal that is lacking under hypoxic treatment alone. At the molecular level, DNA damage induces the interaction of p53 with the transcriptional activator p300 as well as with the transcriptional corepressor mSin3A. In contrast, hypoxia primarily induces an interaction of p53 with mSin3A, but not with p300. Pretreatment of cells with an inhibitor of histone deacetylases that relieves transcriptional repression resulted in a significant reduction of p53-dependent transrepression and hypoxia-induced apoptosis. These results led us to propose a model in which different cellular pools of p53 can modulate transcriptional activity through interactions with transcriptional coactivators or corepressors. Genotoxic stress induces both kinds of interactions, whereas stresses that lack a DNA damage component as exemplified by hypoxia primarily induce interaction with corepressors. However, inhibition of either type of interaction can result in diminished apoptotic activity.

p53 protein accumulation and colonic adenoma recurrence

1999 ◽  
Vol 11 (5) ◽  
pp. 547-552 ◽  
Author(s):  
Konstantinos Triantafyllou ◽  
Gregorios A. Paspatis ◽  
Adamantia Zizi ◽  
George V. Papatheodoridis ◽  
Maria Tzouvala ◽  
...  
Keyword(s):  
P53 Protein ◽  
Protein Accumulation ◽  
Colonic Adenoma ◽  
Adenoma Recurrence

p53 Immunoexpression in Carcinomas Arising in Pleomorphic Adenoma

1996 ◽  
Vol 3 (4) ◽  
pp. 257-262 ◽  
Author(s):  
Joaninha Costa Rosa ◽  
Isabel Fonseca ◽  
Ana Félix ◽  
Jorge Soares
Keyword(s):  
Pleomorphic Adenoma ◽  
P53 Protein ◽  
P53 Gene ◽  
Tumor Grade ◽  
Undifferentiated Carcinoma ◽  
Protein Accumulation ◽  
Low Grade ◽  
Histologic Type ◽  
Epithelial Myoepithelial Carcinoma ◽  
Invasive Carcinomas

p53 protein immunoexpression was evaluated in 17 invasive carcinomas arising in pleomorphic adenoma and correlated with the histologic type and tumor grade. Ten tumors had one malignant histologic component: adenocarcinoma NOS (not otherwise specified) (five), undifferentiated carcinoma (two), malignant myoepithelioma (one), epithelial-myoepithelial carcinoma (one), and malignant oncocytoma (one). In the remaining cases, there was a coexistence of areas of adenocarcinoma (seven), adenosquamous (two), epithelial-myoepithelial (two), adenoid cystic (two), undifferentiated carcinoma (one), and low-grade polymorphous adenocarcinoma (one). p53 positivity was found within adenocarcinoma NOS (three) and adenosquamous carcinoma (two) components of four cases. Tumor areas showing low-grade histology, either mono- or bidifferentiated carcinomas, were always negative in this series, in keeping with previous observations on primary neoplasms of the same histologic type. The benign component of the neoplasms was also found to be consistently negative. The results point to a preferential association of the p53 gene dysfunction and its protein accumulation with the malignant transformation of pleomorphic adenomas into salivary adenocarcinomas with features of high-grade malignancy.

p53 protein accumulation and p53 gene mutation in colorectal cancer

2000 ◽  
Vol 6 (4) ◽  
pp. 275-279 ◽  
Author(s):  
Anna Nasierowska-Guttmejer ◽  
Lech Trzeciak ◽  
Marek P. Nowacki ◽  
Jerzy Ostrowski
Keyword(s):  
Colorectal Cancer ◽  
Gene Mutation ◽  
P53 Protein ◽  
P53 Gene ◽  
Protein Accumulation ◽  
P53 Gene Mutation

K-ras Mutation and p53 Protein Accumulation in Intraductal Mucin-Hypersecreting Neoplasms of the Pancreas

Pancreas ◽  
1996 ◽  
Vol 12 (4) ◽  
pp. 362-368 ◽  
Author(s):  
Kennichi Satoh ◽  
Tooru Shimosegawa ◽  
Shigeki Moriizumi ◽  
Masaru Koizumi ◽  
Takayoshi Toyota
Keyword(s):  
P53 Protein ◽  
Protein Accumulation ◽  
Ras Mutation
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