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Signification of Protein p-53 Isoforms in CLL

The broad spectrum of phenotypes of P53 gene mutations cancer is supported by the fact that the p53 protein isoforms have different cellular mechanisms of prevention against cancer. Acetylation of p53 and phosphorilation is an important means of post-translational modifications and is indispensable for its activation that is a reversible enzymatic process. The both acetylation and deacetylation of p53 protein are involved in the fine regulation of cellular responses to DNA damage.

Signification of Protein p-53 Isoforms in CLL Aurelian Udristioiu¹, Delia-Nica Badea² ¹Molecular Biology, Faculty of Medicine, Titu Maiorescu University, Bucharest, Romania, ² Constantin Brancusi University, Faculty of Medical Science and Behaviors, City Targu Jiu, Romania Chronic Lymphocytic Leukemia, (CLL), occurs in middle aged and elderly person, affecting men to women in approximately 2/1. Many patients are asymptomatic when the disease is diagnosed. Patients with minimal evidence of disease, example, lymphocytosis only, is considered to be early stage of disease, while those demonstrating compromise of bone morrow function as anemia or thrombocytopenia, are in advanced stages. Research has shown that this restoration of function of the protein p-53 can result in regression of certain cancer cells without damaging other cells. In recent years was proved that the best technique in the investigation of malignant lymphocytes is the Fluorescence in situ hybridization (FISH). FISH technique allows the detection and chromosomal rearrangements complex. The principle of this method consists in attaching to the target sequence a single-stranded DNA probes (about 40 kb) fluorescently labeled on the basis of the complementary with a target sequence of a chromosome. The method is used to identify the chromosomal abnormalities and its numerical and structural sites. The broad spectrum of phenotypes of P53 gene mutations cancer is supported by the fact that the p53 protein isoforms have different cellular mechanisms of prevention against cancer. Acetylation of p53 and phosphorilation is an important means of post-translational modifications and is indispensable for its activation that is a reversible enzymatic process. Mutations in P-53 gene can give rise to different isoforms protein p-53, preventing their overall functionality in different cellular mechanisms and thereby extending the cancer phenotype from mild to severe. P-53 protein plays an important role in the regulation of glycolysis, which is demonstrated experimentally. Most research seem to indicate that, in the light of its role as a tumor suppressor p53 is able to drop Glycolysis [7]. This activity can be regarded as an attempt to counter the acquisition of aerobic Glycolysis p53 usually associated with cancer cells. Of major concern, p53 protein has been identified as an important regulator of glucose transport, and was repressing transcription was shown both receptors GLUT1. By contrast, p-53 mutant does not affects GLUT1 and GLUT4 receptor activity. Glucose, by Warburg effect, maintains the stability of the mutant p53 gene which promotes cancer cell growth and generates a positive regulatory loop. This appetite for glucose in the cancer cell, identifies potential therapy of malignant disease, which is currently undergoing extensive investigation. New Cancer Therapy Recent studies have suggested strong cross-talk between histone modifications, translational activity and DNA methylation status. Treatments with methylation-specific agents are used in combination with conventional chemotherapy treatment anti-neoplastic. Somatic gene therapy has become a mass of research in clinical trials using a therapeutic DNA to treat diseases. In recent studies included for treating CLL method. Deletion of the P53 gene and mutations in identifying regions of chromosome 17 of hematologic malignancy is important because these mutations have an impact on the clinical management of patients and require an adjustment of adequate therapeutic attitude in a personalized medicine. Personalized treatments to be applied by a combination of diagnostic tools, knowledge databases and therapeutic drugs.

Keywords

Fluorescence in situ hybridization, DNA technology, phenotypes of P53 gene

Countries

Romania