Disease	Score

Substances	Interaction	Organism	Category

Substances	Interaction	Organism	Category

Somatic TP53 gene mutations have been found in some cases of bladder cancer. Most of these mutations change single amino acids in p53 . The altered protein cannot bind to DNA, preventing it from effectively regulating cell growth and division. As a result, DNA damage accumulates in cells, which can allow them to grow and divide in an uncontrolled way to form a cancerous tumor. Mutations in the TP53 gene may help predict whether bladder cancer will progress and spread to nearby tissues, and whether the disease will recur after treatment. breast cancer Inherited changes in the TP53 gene greatly increase the risk of developing breast cancer, as well as several other forms of cancer, as part of a rare cancer syndrome called Li-Fraumeni syndrome (described below). These mutations are thought to account for only a small fraction of all breast cancer cases. Noninherited (somatic) mutations in the TP53 gene are much more common than inherited mutations, occurring in 20 to 40 percent of all breast cancers. These somatic mutations are acquired during a person's lifetime and are present only in cells that become cancerous. The cancers associated with somatic mutations do not occur as part of a cancer syndrome. Most of these mutations change single protein building blocks (amino acids) in the p53 protein, which reduces or eliminates the protein's tumor suppressor function. Because the altered protein is less able to regulate cell growth and division, DNA damage can accumulate. This damage may contribute to the development of a cancerous tumor by allowing cells to grow and divide in an uncontrolled way. Compared with breast cancers without TP53 gene mutations, tumors with these genetic changes tend to have a poorer prognosis. They are more likely to be aggressive, to be resistant to treatment with certain anti-cancer drugs and radiation, and to come back (recur) after treatment. cholangiocarcinoma Genetics Home Reference provides information about cholangiocarcinoma. head and neck squamous cell carcinoma Somatic mutations in the TP53 gene have been found in nearly half of all head and neck squamous cell carcinomas (HNSCC). This type of cancerous tumor occurs in the moist lining of the mouth, nose, and throat. Most of the TP53 gene mutations involved in HNSCC change single amino acids in p53; these changes impair the protein's function. Without functioning p53, DNA damage builds up in cells, and they can continue to divide without control, leading to tumor formation. Li-Fraumeni syndrome Although somatic mutations in the TP53 gene are found in many types of cancer, Li-Fraumeni syndrome appears to be the only cancer syndrome associated with inherited mutations in this gene. This condition greatly increases the risk of developing several types of cancer, particularly in children and young adults. At least 140 different mutations in the TP53 gene have been identified in individuals with Li-Fraumeni syndrome. Many of the mutations associated with Li-Fraumeni syndrome change single amino acids in the part of the p53 protein that binds to DNA. Other mutations delete small amounts of DNA from the gene. Mutations in the TP53 gene lead to a version of p53 that cannot regulate cell growth and division effectively. Specifically, the altered protein is unable to trigger apoptosis in cells with mutated or damaged DNA. As a result, DNA damage can accumulate in cells. Such cells may continue to divide in an uncontrolled way, leading to the growth of tumors. ovarian cancer Somatic TP53 gene mutations are common in ovarian cancer, occurring in almost half of ovarian tumors. These mutations result in a p53 protein that is less able to control cell growth and division, contributing to the development of a cancerous tumor. other cancers Somatic mutations in the TP53 gene are the most common genetic changes found in human cancer, occurring in about half of all cancers. In addition to the cancers described above, somatic TP53 gene mutations have been identified in several types of brain tumor, colorectal cancer, liver cancer, lung cancer, a type of bone cancer called osteosarcoma, a cancer of muscle tissue called rhabdomyocarcinoma, and a cancer called adrenocortical carcinoma that affects the outer layer of the adrenal glands (small hormone-producing glands on top of each kidney). Most TP53 mutations change single amino acids in the p53 protein, which leads to the production of an altered version of the protein that cannot control cell growth and division effectively. As a result, cells can grow and divide in an unregulated way, which can lead to cancerous tumors.

The TP53 gene provides instructions for making a protein called tumor protein p53 (or p53). This protein acts as a tumor suppressor, which means that it regulates cell division by keeping cells from growing and dividing too fast or in an uncontrolled way. The p53 protein is located in the nucleus of cells throughout the body, where it attaches (binds) directly to DNA. When the DNA in a cell becomes damaged by agents such as toxic chemicals, radiation, or ultraviolet (UV) rays from sunlight, this protein plays a critical role in determining whether the DNA will be repaired or the damaged cell will self-destruct (undergo apoptosis). If the DNA can be repaired, p53 activates other genes to fix the damage. If the DNA cannot be repaired, this protein prevents the cell from dividing and signals it to undergo apoptosis. By stopping cells with mutated or damaged DNA from dividing, p53 helps prevent the development of tumors. Because p53 is essential for regulating cell division and preventing tumor formation, it has been nicknamed the "guardian of the genome."

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

The following transcription factors affect gene expression:

• NF-kappaB
• p53
• AhR
• NF-kappaB1
• c-Myc
• E2F-1
• YY1

Tissue specificity:

Ubiquitous. Isoforms are expressed in a wide range of normal tissues but in a tissue-dependent manner. Isoform 2 is expressed in most normal tissues but is not detected in brain, lung, prostate, muscle, fetal brain, spinal cord and fetal liver. Isoform 3 is expressed in most normal tissues but is not detected in lung, spleen, testis, fetal brain, spinal cord and fetal liver. Isoform 7 is expressed in most normal tissues but is not detected in prostate, uterus, skeletal muscle and breast. Isoform 8 is detected only in colon, bone marrow, testis, fetal brain and intestine. Isoform 9 is expressed in most normal tissues but is not detected in brain, heart, lung, fetal liver, salivary gland, breast or intestine.

Induction:

Up-regulated in response to DNA damage. Isoform 2 is not induced in tumor cells in response to stress.

Cofactor:

Binds 1 zinc ion per subunit.

Molecular Function:

• Rna Polymerase Ii Regulatory Region Sequence-Specific Dna Binding
• Rna Polymerase Ii Transcription Factor Activity, Sequence-Specific Dna Binding
• Core Promoter Sequence-Specific Dna Binding
• Rna Polymerase Ii Transcription Factor Binding
• Transcriptional Activator Activity, Rna Polymerase Ii Transcription Regulatory Region Sequence-Specific Binding
• Protease Binding
• P53 Binding
• Dna Binding
• Chromatin Binding
• Damaged Dna Binding
• Double-Stranded Dna Binding
• Transcription Factor Activity, Sequence-Specific Dna Binding
• Copper Ion Binding
• Atp Binding
• Transcription Factor Binding
• Zinc Ion Binding
• Enzyme Binding
• Protein Kinase Binding
• Protein Phosphatase Binding
• Receptor Tyrosine Kinase Binding
• Ubiquitin Protein Ligase Binding
• Histone Acetyltransferase Binding
• Identical Protein Binding
• Sequence-Specific Dna Binding
• Protein Self-Association
• Transcription Regulatory Region Dna Binding
• Protein Heterodimerization Activity
• Protein N-Terminus Binding
• Chaperone Binding
• Protein Phosphatase 2a Binding

Biological Processes:

• Base-Excision Repair
• Cell Aging
• Cell Cycle Arrest
• Cell Differentiation
• Cell Proliferation
• Cellular Protein Localization
• Cellular Response To Dna Damage Stimulus
• Cellular Response To Glucose Starvation
• Cellular Response To Hypoxia
• Cellular Response To Ionizing Radiation
• Cellular Response To Uv
• Chromatin Assembly
• Circadian Behavior
• Determination Of Adult Lifespan
• Dna Damage Response, Signal Transduction By P53 Class Mediator
• Dna Damage Response, Signal Transduction By P53 Class Mediator Resulting In Cell Cycle Arrest
• Dna Damage Response, Signal Transduction By P53 Class Mediator Resulting In Transcription Of P21 Class Mediator
• Dna Strand Renaturation
• Entrainment Of Circadian Clock By Photoperiod
• Er Overload Response
• Intrinsic Apoptotic Signaling Pathway
• Intrinsic Apoptotic Signaling Pathway By P53 Class Mediator
• Intrinsic Apoptotic Signaling Pathway In Response To Dna Damage By P53 Class Mediator
• Mitotic G1 Dna Damage Checkpoint
• Multicellular Organism Development
• Negative Regulation Of Apoptotic Process
• Negative Regulation Of Cell Growth
• Negative Regulation Of Cell Proliferation
• Negative Regulation Of Fibroblast Proliferation
• Negative Regulation Of Helicase Activity
• Negative Regulation Of Telomerase Activity
• Negative Regulation Of Transcription, Dna-Templated
• Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
• Nucleotide-Excision Repair
• Oligodendrocyte Apoptotic Process
• Oxidative Stress-Induced Premature Senescence
• Positive Regulation Of Apoptotic Process
• Positive Regulation Of Cell Cycle Arrest
• Positive Regulation Of Execution Phase Of Apoptosis
• Positive Regulation Of Gene Expression
• Positive Regulation Of Histone Deacetylation
• Positive Regulation Of Intrinsic Apoptotic Signaling Pathway
• Positive Regulation Of Neuron Apoptotic Process
• Positive Regulation Of Peptidyl-Tyrosine Phosphorylation
• Positive Regulation Of Protein Export From Nucleus
• Positive Regulation Of Protein Insertion Into Mitochondrial Membrane Involved In Apoptotic Signaling Pathway
• Positive Regulation Of Protein Oligomerization
• Positive Regulation Of Reactive Oxygen Species Metabolic Process
• Positive Regulation Of Release Of Cytochrome C From Mitochondria
• Positive Regulation Of Thymocyte Apoptotic Process
• Positive Regulation Of Transcription, Dna-Templated
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter In Response To Endoplasmic Reticulum Stress
• Proteasome-Mediated Ubiquitin-Dependent Protein Catabolic Process
• Protein Complex Assembly
• Protein Localization
• Protein Sumoylation
• Protein Tetramerization
• Ras Protein Signal Transduction
• Regulation Of Apoptotic Process
• Regulation Of Cell Cycle G2/M Phase Transition
• Regulation Of Mitochondrial Membrane Permeability
• Regulation Of Signal Transduction By P53 Class Mediator
• Regulation Of Transcription, Dna-Templated
• Replicative Senescence
• Response To Antibiotic
• Response To Gamma Radiation
• Response To X-Ray
• Viral Process

Drug Bank:

• Acetylsalicylic Acid

*synonyms