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Repair or perish – the role of p53 protein in a cell’s life
Affiliations- Independent Laboratory of Cytogenetics, Maria Sklodowska-Curie Institute – Oncology Center, Warsaw, Poland
- Laboratory of Genetic and Molecular Diagnostics, Maria Sklodowska-Curie Institute – Oncology Center, Warsaw, Poland
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Abstract
The p53 protein is one of the most important suppressors of neoplastic transformation. It regulates transcription of multiple genes and interacts directly with other proteins. It plays a significant role in the most important processes that take place in the cell, including: DNA repair, cell cycle and programmed cell death – apoptosis. Loss of its proper function leads to a disturbance of the mechanisms controlling cell proliferation and survival, which contributes to the development of neoplasms.
The TP53 gene is called the guardian of the genome. Its mutations occur in a large percentage of tumors. They most often concern sequences that encode the DNA-binding domain (exons 5–8). The TP53 gene, together with the TP63 and TP73 genes, belongs to the oldest evolutionary family of cancer transformation suppressors. Its product, a full length p53 protein, consists of five domains and a flexible consolidator region and functions as a homotetramer. The regulation of p53 activity is caused by MDM2 protein, which contributes to proteasomal degradation of the suppressor.
This review deals with the most important aspects of the regulation of cell activity by p53 protein. It describes the structure of p53 protein and the associated therapeutic possibilities.
Abstract
The p53 protein is one of the most important suppressors of neoplastic transformation. It regulates transcription of multiple genes and interacts directly with other proteins. It plays a significant role in the most important processes that take place in the cell, including: DNA repair, cell cycle and programmed cell death – apoptosis. Loss of its proper function leads to a disturbance of the mechanisms controlling cell proliferation and survival, which contributes to the development of neoplasms.
The TP53 gene is called the guardian of the genome. Its mutations occur in a large percentage of tumors. They most often concern sequences that encode the DNA-binding domain (exons 5–8). The TP53 gene, together with the TP63 and TP73 genes, belongs to the oldest evolutionary family of cancer transformation suppressors. Its product, a full length p53 protein, consists of five domains and a flexible consolidator region and functions as a homotetramer. The regulation of p53 activity is caused by MDM2 protein, which contributes to proteasomal degradation of the suppressor.
This review deals with the most important aspects of the regulation of cell activity by p53 protein. It describes the structure of p53 protein and the associated therapeutic possibilities.
Keywords
suppressor genes, p53 protein structure; p53; p53 vs. cell activity regulation
About this articleTitle
Repair or perish – the role of p53 protein in a cell’s life
Journal
Nowotwory. Journal of Oncology
Issue
Article type
Review paper
Pages
168-178
Published online
2019-12-31
Page views
1140
Article views/downloads
1098
DOI
Bibliographic record
Nowotwory. Journal of Oncology 2019;69(5-6):168-178.
Keywords
suppressor genes
p53 protein structure
p53
p53 vs. cell activity regulation
Authors
Magdalena Kulesza
Agnieszka Dansonka-Mieszkowska
Barbara Pieńkowska-Grela