Tumor Growth
John Melford in Pocket Guide to Cancer, 2017
Commonly referred to as “the guardian of the genome,” p53 plays a key role in regulating cell division and preventing tumor formation. It is coded for by the tumor protein 53 (TP53) gene. In the cell nucleus, p53 binds directly to DNA, which makes it a transcription factor. It responds to inputs from other proteins that act as sensors of stress inside a cell, such as DNA damage, as well as low levels of oxygen and growth-promoting signals. When it receives a signal that the DNA of a cell is damaged, p53 responds by activating repair enzymes to fix it. If they are unable to do so within a limited timeframe, cell division ceases, and the cell is instructed to commit suicide. Thus, under circumstances of overwhelming damage to cellular subsystems, p53 triggers cell death. By the elimination of cells with damaged DNA, p53 suppresses the development of tumors. The inactivation of p53 is common in a high percentage of tumors.
The Role of Nanoparticles in Cancer Therapy through Apoptosis Induction
Hala Gali-Muhtasib, Racha Chouaib in Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
Nanoparticles (NPs) can induce oxidative stress in cells through diverse mechanisms: first, by a direct generation of ROS; second, by an indirect generation of ROS and reactive nitrogen species (RNS) through stimulating inflammatory cells [51]; third, by the indirect changes in mitochondrial integrity through NADPH oxidase or cellular calcium homeostasis; and last, by ROS generation through releasing ions or soluble compounds [45]. Any mechanism that leads to ROS production ultimately leads to damage to DNA and proteins as well as destruction of organelles such as mitochondria. The damaged mitochondria leads to the activation of apoptosis [54, 60]. The main operation of ROS in various cellular mechanisms is involved in cell cycle regulation, proliferation, self-renewal, differentiation, and apoptosis. The primary function of p53 as a tumor suppressor, upon DNA damage, is to induce cell cycle arrest and to repair the damage. If the damage cannot be repaired, apoptosis is initiated [38].
Proto-Oncogene and Onco-Suppressor Gene Expression
Enrique Pimentel in Handbook of Growth Factors, 2017
The notion that p53 is essential for cell proliferation is supported by the observation that microinjection of a monoclonal antibody to p53 into the nuclei of quiescent Swiss 3T3 cells inhibits serum-induced entry of the cells into the S phase of the cycle.362,363 Introduction of DNA constructs encoding p53-specific antisense RNA into transformed and nontransformed mouse cells results in the complete cessation of the proliferation of these cells.364 The results from different studies support the idea that one function of the p53 protein is to activate the transcription of genes involved in the suppression of cell proliferation. The antiproliferative effects of p53 are related to the acquisition of a unique conformational state associated with an increased level of phosphorylation of the protein.365 Phosphorylation of wild-type and mutant p53 proteins at specific amino acid residues depends on associated protein kinases.366 Protein kinase C phosphorylates the p53 protein both in vivo and in vitro, and interaction of p53 with SI00b (a member of the SI00 protein family involved in cell cycle progression and cell differentiation) is inhibited by p53 phosphorylation by protein kinase C.367
Development of molecular intervention strategies for B-cell lymphoma
Published in Expert Review of Hematology, 2021
Wenyujing Zhou, Weihong Chen
TP53, an anti-oncogene, is mainly concentrated on the exon 5–8 DNA binding domain (DBD) [3]. TP53 is located at chromosome 17q13.1 and spans 19,144 nucleotides, 2586 of which are transcribed into the TP53 mRNA. TP53 codes for a tumor suppressor protein, cellular tumor antigen p53. The p53 regulates the expression of several genes involved in cell cycle arrest, apoptosis, senescence, DNA repair, and changes in metabolism. The p53 elicits its anti-cancer roles through several mechanisms. (1) When DNA is damaged, p53 activates DNA repair and blocks the progression of the cell cycle, prolonging the G1/S phase thereby providing more time for the DNA repair proteins to repair the damaged DNA. Once the damage is repaired, p53 allows the progression of cell growth. (2) If the DNA damage cannot be repaired, p53 triggers apoptosis and thereby prevents the cell from carrying abnormal genetic information.
miR-34a predicts the prognosis of advanced-stage external auditory canal squamous cell carcinoma
Published in Acta Oto-Laryngologica, 2022
Naotaro Akiyama, Tomomi Yamamoto-Fukuda, Hiromi Kojima
Generally, endogenous p53 acts as a tumor suppressor and is expressed in the nuclei of all normal cells [15]. Endogenous p53 is usually not detectable in IHC due to a very short half-life [15]. On the other hand, mutated p53 exhibits a prolonged half-life, which accumulates within the cell nuclei and can be detected in the IHC [15]. Once it acquires the mutation, mutant p53 implies loss of p53 function and induces tumor development [15]. In previous studies, up-regulation of mutant p53 was reported in many cancers [16]. However, positive cells of p53 were not detected in the case of T3, Stage IV, and scarcely detected in the case of T4, Stage IV in this study. Interestingly, the expression levels of Ki67 did not show a tendency to correlate with the expression levels of p53 in the EACSCC specimens. In other words, the expression level of p53 varied regardless of the stage of EACSCC in the cases of this study. It also has been reported that p53 heterogeneity is observed in many cancers, ranging from intense staining of all tumor cell nuclei to a complete absence of IHC [17], which data supports our results.
Modulating effect of hesperetin on the molecular expression pattern of apoptotic and cell proliferative markers in 7,12-dimethylbenz(a)anthracene-induced oral carcinogenesis
Published in Archives of Physiology and Biochemistry, 2020
Sukumar Babukumar, Veerasamy Vinothkumar, Duraisamy Ramachandhiran
The molecular approach of cancer chemoprevention study utilises apoptotic and cell proliferative proteins and focus on the investigation of the new anticancer agent from a natural source. The tumour suppressor protein p53 is the guardian of the genome and is involved in the regulation of apoptosis, gene amplification and DNA recombination. Mutated-p53 is strongly implicated in several carcinogenesis through the defect in cell-cycle progression and protects cells from apoptosis (Hientz et al.2017). Cyclin-D1 is an important cell-cycle protein that regulates the cell cycle from G1 to S phase through cyclin-dependent kinases. Dysfunction of cell cycle leads to overexpression of cyclin-D1 associated with many cancer types including oral cancer (Duronio and Xiong 2013). Mitochondria by releasing proapoptotic factors contribute to both the caspase-dependent and independent pathways of apoptosis (Alam et al. 2011). In addition initiator (casp-9) and effector (casp-3) caspases are responsible for the stimulation of apoptosis. Decreased caspases expression may prevent the cell from apoptosis that leads to tumorigenesis (Fogarty and Bergmann 2017).
Related Knowledge Centers
- Chromosome 17
- Exon
- Genome
- Protein Isoform
- Tumor Suppressor Gene
- Cancer
- Tumor Antigen
- Uniprot
- Hp53Int1
- Sequence Homology