Cholera toxin animation


Cholera toxin (sometimes abbreviated to CTX, Ctx, or CT) is a protein complex secreted by the bacterium Vibrio cholerae.CTX is responsible for the harmful effects of cholera infection.

Mechanism of action

The cholera toxin contains two major parts. The first is a pentameric protein that binds to the surface of the intestinal epithelium. The second is an ADP-ribosylation enzyme which ribosylates the Gs alpha subunit of the heterotrimeric G protein resulting in constitutive cAMP production. This in turn lead to secretion of chloride and water into the lumen of the intestine resulting in rapid dehydration.

Structure

The cholera toxin is an oligomeric complex made up of six protein subunits: a single copy of the A subunit, and five copies of the B subunit. Its three-dimensional structure was determined using X-ray crystallography by Zhang et al. in 1995.




The five B subunits—each weighing 12 kDa, and all coloured blue in the accompanying figure—form a five-membered ring. The A subunit has two important segments. The A1 portion of the chain (CTA1, red) is a globular enzyme payload that ADP-ribosylates G proteins, while the A2 chain (CTA2, orange) forms an extended alpha helix which seats snugly in the central pore of the B subunit ring.

This structure is similar in shape, mechanism, and sequence to the heat-labile enterotoxin secreted by some strains of the Escherichia coli bacterium.

Synthesis
Once secreted, the B subunit ring of CTX will bind to GM1 gangliosides on the surface of the host's cells. After binding takes place, the entire CTX complex is internalised by the cell and the CTA1 chain is released by the reduction of a disulfide bridge.

CTA1 is then free to bind with a human partner protein called ADP-ribosylation factor 6 (Arf6); binding to Arf6 drives a change in the conformation (the shape) of CTA1 which exposes its active site and enables its catalytic activity.

The CTA1 fragment catalyses ADP ribosylation from NAD to the regulatory component of adenylate cyclase, thereby activating it. Increased adenylate cyclase activity increases cyclic AMP (cAMP) synthesis causing massive fluid and electrolyte efflux, resulting in diarrhea.


Applications

Because the B subunit appears to be relatively non-toxic, researchers have found a number of applications for it in cell and molecular biology.

It has been used to trace neurons.

GM1 gangliosides are found in lipid rafts on the cell surface. B subunit complexes labelled with fluorescent tags or subsequently targeted with antibodies can be used to identify rafts.

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Nanoparticles in AIDS

Digestive Enzymes


Digestive enzymes are enzymes in the alimentary canal that break down food so that the organism can absorb it. The main sites of action are the oral cavity, the stomach, the duodenum and the jejunum. They are secreted by different glands: the salivary glands, the glands in the stomach, the pancreas, and the glands in the small intestines. Oral cavity In the oral cavity, salivary glands secrete ptyalin. It is a type of α-amylase, which digests starch into small segments of multiple sugars and into the individual soluble sugars. Secreted by small and large salivary glands.

  Subscribe in a reader Salivary glands also secrete lysozyme, which kills bacteria but is not classified as a digestive enzyme. Stomach The enzymes that get secreted in the stomach are called gastric enzymes. These are the following: * Pepsin is the main gastric enzyme. As it breaks proteins into smaller peptide fragments, it is a peptidase. * Gelatinase, degrades type I and type V gelatin and type IV and V collagen, which are proteoglycans in meat. * Gastric amylase degrades starch, but is of minor significance. * Gastric lipase is a tributyrase by its biochemical activity, as it acts almost exclusively on tributyrin, a butter fat enzyme.

Pancreatic enzymes The pancreas is the main digestive gland in our body. It secretes the enzymes: * Trypsin, is a peptidase, that breaks down peptides in the small intestine. * Chymotrypsin, also a peptidase * Steapsin, degrades triglycerides into fatty acids and glycerol. * Carboxypeptidase, splits peptide fragments into individual amino acids. It is a protease. * Several elastases that degrade the protein elastin and some other proteins. * Several nucleases that degrade nucleic acids, like DNAase and RNAase * Pancreatic amylase that, besides starch, glycogen and cellulose, degrades most other carbohydrates. * Bile from the liver, which emulsifies fat, allowing more efficient use of lipases in the duodenum; in converting lipids to their component fatty acid and glycerol molecules Proper small intestine enzymes * Several peptidases. * The jejunum and ileum secretes a juice called succus entericus which contains the following: Six types of enzymes degrade disaccharides into monosaccharides: * Sucrase, which breaks down sucrose into glucose and fructose * Maltase, which breaks down maltose into glucose. * Isomaltase, which breaks down maltose and isomaltose * Lactase, which breaks down lactose into glucose and galactose * Intestinal lipase, which breaks down fatty acids The small intestine receives lipase, trypsin and amylase from the pancreas. They are transported from the pancreas to the duodenum through the pancreatic duct. Protein, fats and starch are broken down into smaller molecules. However, they are not fully broken down yet. This causes the enzymes of the small intestine to act upon them. These enzymes include peptidase, which breaks down peptides into amino acids and the enzyme maltase acts upon maltose which produces glucose. These molecules are absorbed by the villi in the small intestine and according to the molecule they are either absorbed by the lacteal or blood capillaries.

Taxol Mechanism of action

Taxol (paclitaxel)is anticancer drug which was produced natually .Taxol is a mitotic inhibitor used in cancer chemotherapy. It was discovered in a National Cancer Institute program at the Research Triangle Institute in 1967 when Monroe E. Wall and Mansukh C. Wani isolated it from the bark of the Pacific yew tree, Taxus brevifolia and named it 'taxol'.
Paclitaxel is now used to treat patients with lung, ovarian, breast cancer, head and neck cancer, and advanced forms of Kaposi's sarcoma. Paclitaxel is also used for the prevention of restenosis.

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The anti-cancer drug Taxol works by interfering with processes within cells. The way in which Taxol binds to microtubule and prevents cell division is shown in this animation.

Taxol works by interfering with normal microtubule breakdown during cell division. Together with docetaxel, it forms the drug category of the taxanes. It was the subject of a notable total synthesis by Robert A. Holton.
Mechanism of action
Taxol interferes with the normal function of microtubule breakdown. Whereas drugs like colchicine cause the depolymerization of microtubules, paclitaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell's ability to use its cytoskeleton in a flexible manner. Specifically, paclitaxel binds to the β subunit of tubulin. Tubulin is the "building block" of microtubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a mechanism to transport other cellular components. For example, during mitosis, microtubules position the chromosomes during their replication and subsequent separation into the two daughter-cell nuclei.

Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.
In addition to stabilizing microtubules paclitaxel may act as a molecular mop by sequestering free tubulin effectively depleting the cells supply of tubulin monomers and/or dimers. This activity may trigger the aforementioned apoptosis.
One common characteristic of most cancer cells is their rapid rate of cell division. In order to accommodate this, the cytoskeleton of a cell undergoes extensive restructuring. Paclitaxel is an effective treatment for aggressive cancers because it adversely affects the process of cell division by preventing this restructuring. Cancer cells are also destroyed by the aforementioned anti-Bcl-2 mechanism. Other cells are also affected adversely, but since cancer cells divide much faster than non-cancerous cells, they are far more susceptible to paclitaxel treatment.

Red Blood Cells

Red blood cells are the most common type of blood cell and the vertebrate body's principal means of delivering oxygen from the lungs or gills to body tissues via the blood.Red blood cells are also known as RBCs, red blood corpuscles (an archaic term), haematids or erythrocytes.



Erythrocytes consist mainly of hemoglobin, a complex molecule containing heme groups whose iron atoms temporarily link to oxygen molecules in the lungs or gills and release them throughout the body. Oxygen can easily diffuse through the red blood cell's cell membrane. Hemoglobin also carries some of the waste product carbon dioxide back from the tissues. (In humans, less than 2% of the total oxygen, and most of the carbon dioxide, is held in solution in the blood plasma). A related compound, myoglobin, acts to store oxygen in muscle cells.

The color of erythrocytes is due to the heme group of hemoglobin. The blood plasma alone is straw-colored, but the red blood cells change color depending on the state of the hemoglobin: when combined with oxygen the resulting oxyhemoglobin is scarlet, and when oxygen has been released the resulting deoxyhemoglobin is darker, appearing bluish through the vessel wall and skin. Pulse oximetry takes advantage of this color change to directly measure the arterial blood oxygen saturation using colorimetric techniques.

The sequestration of oxygen carrying proteins inside specialized cells (rather than having them dissolved in body fluid) was an important step in the evolution of vertebrates; it allows for less viscous blood, higher concentrations of oxygen, and better diffusion of oxygen from the blood to the tissues. The size of erythrocytes varies widely among vertebrate species; erythrocyte width is on average about 25% larger than capillary diameter and it has been hypothesized that this improves the oxygen transfer from erythrocytes to tissues.


The only known vertebrates that don't use erythrocytes for oxygen transport are the ice fishes (family Channichthyidae); they live in very oxygen rich cold water and transport oxygen freely dissolved in their blood.

In 2007 it was reported that erythrocytes also play a part in the body's immune response: when lysed by pathogens such as bacteria, their hemoglobin releases free radicals that break down the pathogen's cell wall and membrane, killing it.


Mammalian erythrocytes
Erythrocytes in mammals are anucleate when mature, meaning that they lack a cell nucleus and as a result, have no DNA. Red blood cells have nuclei during early phases of development, but extrude them as they mature in order to provide more space for hemoglobin. In comparison, the erythrocytes of nearly all other vertebrates have nuclei; the only known exception being salamanders of the Batrachoseps genus.Mammalian erythrocytes also lose their other organelles such as their mitochondria. As a result, red blood use none of the oxygen they transport; they produce the energy carrier ATP by fermentation, via glycolysis of glucose followed by lactic acid production. Furthermore, red cells do not have an insulin receptor and thus glucose uptake is not regulated by insulin. Because of the lack of nucleus and organelles, the red blood cells cannot synthesize any RNA, and consequently they cannot divide or repair themselves.

Mammalian erythrocytes are biconcave disks: flattened and depressed in the center, with a dumbbell-shaped cross section. This shape (as well as the loss of organelles and nucleus) optimizes the cell for the exchange of oxygen with its surroundings. The cells are flexible so as to fit through tiny capillaries, where they release their oxygen load. Erythrocytes are circular, except in the camel family Camelidae, where they are oval.

In large blood vessels, red blood cells sometimes occur as a stack, flat side next to flat side. This is known as rouleaux formation, and it occurs more often if the levels of certain serum proteins are elevated, as for instance during inflammation.

The spleen acts as a reservoir of red blood cells, but this effect is somewhat limited in humans. In some other mammals such as dogs and horses, the spleen sequesters large numbers of red blood cells which are dumped into the blood during times of exertion stress, yielding a higher oxygen transport capacity.

Human erythrocytes

The diameter of a typical human erythrocyte disk is 6–8 µm, much smaller than most other human cells. A typical erythrocyte contains about 270 million hemoglobin molecules, with each carrying four heme groups.

Adult humans have roughly 2–3 × 1013 red blood cells at any given time (women have about 4 to 5 million erythrocytes per microliter (cubic millimeter) of blood and men about 5 to 6 million; people living at high altitudes with low oxygen tension will have more). Red blood cells are thus much more common than the other blood particles: There are about 4,000–11,000 white blood cells and about 150,000–400,000 platelets in each microliter of human blood.

The red blood cells of an average adult human male store collectively about 2.5 grams of iron, representing about 65% of the total iron contained in the body.

Life cycle

The process by which red blood cells are produced is called erythropoiesis. Erythrocytes are continuously being produced in the red bone marrow of large bones, at a rate of about 2 million per second. (In the embryo, the liver is the main site of red blood cell production.) The production can be stimulated by the hormone erythropoietin (EPO), synthesised by the kidney; which is used for doping in sports. Just before and after leaving the bone marrow, they are known as reticulocytes which comprise about 1% of circulating red blood cells.

Erythrocytes develop from committed stem cells through reticulocytes to mature erythrocytes in about 7 days and live a total of about 120 days.

The aging erythrocyte undergoes changes in its plasma membrane, making it susceptible to recognition by phagocytes and subsequent phagocytosis in the spleen, liver and bone marrow. Much of the important breakdown products are recirculated in the body. The heme constituent of hemoglobin are broken down into Fe3+ and biliverdin. The biliverdin is reduced to bilirubin, which is released into the plasma and recirculated to the liver bound to albumin. The iron is released into the plasma to be recirculated by a carrier protein called transferrin. Almost all erythrocytes are removed in this manner from the circulation before they are old enough to hemolyze. Hemolyzed hemoglobin is bound to a protein in plasma called haptoglobin which is not excreted by the kidney.

Genetic Transfer

 Genetic Transfer part1 Genetic Transfer part2 Genetic Transfer part 3 Genetic Transfer part 4

First Human Gene Therapy

On September 14, 1990 at the U.S. National Institutes of Health W. French Anderson, M.D., and his colleagues R. Michael Blaese, M.D., C. Bouzaid, M.D., and Kenneth Culver, M.D., performed the first approved gene therapy procedure on four-year old Ashanthi DeSilva. Born with a rare genetic disease called severe combined immunodeficiency (SCID), she lacked a healthy immune system, and was vulnerable to every passing germ or infection. Children with this illness usually develop overwhelming infections and rarely survive to adulthood; a common childhood illness like chickenpox is life-threatening. Ashanthi led a cloistered existence -- avoiding contact with people outside her family, remaining in the sterile environment of her home, and battling frequent illnesses with massive amounts of antibiotics.
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In Ashanthi's gene therapy procedure, doctors removed white blood cells from the child's body, let the cells grow in the lab, inserted the missing gene into the cells, and then infused the genetically modified blood cells back into the patient's bloodstream. Laboratory tests have shown that the therapy strengthened Ashanthi's immune system by 40%; she no longer has recurrent colds, she has been allowed to attend school, and she was immunized against whooping cough. This procedure was not a cure; the white blood cells treated genetically only work for a few months, after which the process must be repeated (VII, Thompson [First] 1993). As of early 2007, she was still in good health, and she was attending college. However, there is no consensus on what portion of her improvement should be attributed to gene therapy versus other treatments. Some would state that the case is of great importance despite its indefinite results, if only because it demonstrated that gene therapy could be practically attempted without adverse consequences.

Although this simplified explanation of a gene therapy procedure sounds like a happy ending, it is little more than an optimistic first chapter in a long story; the road to the first approved gene therapy procedure was rocky and fraught with controversy. The biology of human gene therapy is very complex, and there are many techniques that still need to be developed and diseases that need to be understood more fully before gene therapy can be used appropriately. The public policy debate surrounding the possible use of genetically engineered material in human subjects has been equally complex. Major participants in the debate have come from the fields of biology, government, law, medicine, philosophy, politics, and religion, each bringing different views to the discussion.

Chromosomes

Chromosomes are organized structures of DNA and proteins that are found in cells. A chromosome is a continuous piece of DNA, which contains many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions. The word chromosome comes from the Greek χρῶμα (chroma, color) and σῶμα (soma, body) due to their property of being stained very strongly by some dyes.




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Chromosomes vary extensively between different organisms. The DNA molecule may be circular or linear, and can contain anything from tens of kilobase pairs to hundreds of megabase pairs. Typically eukaryotic cells (cells with nuclei) have large linear chromosomes and prokaryotic cells (cells without defined nuclei) have smaller circular chromosomes, although there are many exceptions to this rule. Furthermore, cells may contain more than one type of chromosome; for example mitochondria in most eukaryotes and chloroplasts in plants have their own small chromosomes.


In eukaryotes, nuclear chromosomes are packaged by proteins into a condensed structure called chromatin. This allows the massively-long DNA molecules to fit into the cell nucleus. The structure of chromosomes and chromatin varies through the cell cycle. Chromosomes may exist as either duplicated or unduplicated—unduplicated chromosomes are single linear strands, while duplicated chromosomes (copied during S phase) contain two copies joined by a centromere. Compaction of the duplicated chromosomes during mitosis and meiosis results in the classic four-arm structure (pictured to the right).

"Chromosome" is a rather loosely defined term. In prokaryotes, a small circular DNA molecule may be called either a plasmid or a small chromosome. These small circular genomes are also found in mitochondria and chloroplasts, reflecting their bacterial origins. The simplest chromosomes are found in viruses: these DNA or RNA molecules are short linear or circular chromosomes that often lack any structural proteins.

Inflammatory Response

The inflammatory response must be actively terminated when no longer needed to prevent unnecessary "bystander" damage to tissues. Failure to do so results in chronic inflammation, cellular destruction, and attempts to heal the inflamed tissue. One intrinsic mechanism employed to terminate inflammation is the short half-life of inflammatory mediators in vivo. They have a limited time frame to affect their target before breaking down into non-functional components, therefore constant inflammatory stimulation is needed to propagate their effects.


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Ihe Inflammatory Response can be triggered by invasion of bacteria,Substances released by bacteiria by damaged cells accumulate in tissue small blood vessels become more premeable and plasma fluids and proteins leakout,plasma protein attack bacteria and attract blood white cells.white blood cell engulf bacteria and help repair damage tissue

p53 Cellular tumor antigen Animation

p53, also known as protein 53 (TP53), is a transcription factor that regulates the cell cycle and hence functions as a tumor suppressor. It is important in multicellular organisms as it helps to suppress cancer. p53 has been described as "the guardian of the genome," "the guardian angel gene," or the "master watchman," referring to its role in conserving stability by preventing genome mutation.


The name p53 is in reference to its apparent molecular mass: it runs as a 53-kilodalton (kDa) protein on SDS-PAGE. But different ways of measuring molecular mass can produce different results. Based on calculations from its amino acid residues, p53's mass is actually only 43.7 kilodaltons. This difference is due to the high number of amino-acid proline residues in the p53 protein which slow p53's migration on SDS-PAGE, thus making it appear larger. This effect is observed with p53 from a variety of species, including humans, rodents, frogs, and fish.


Official protein name: Cellular tumor antigen p53

Synonyms:

Tumor suppressor p53
Phosphoprotein p53
Antigen NY-CO-13

Gene
The human gene that encodes for p53 is TP53. The gene is named TP53 after the protein it codes for (TP53 is another name for p53). Italics are used to distinguish the TP53 gene name from the TP53 protein name. The gene is located on the human chromosome 17 (17p13.1).

The location has also been mapped on other model animals:

  • Mouse - chromosome 11
  • Rat - chromosome 10
  • Dog - chromosome 5
  • Pig - chromosome 12
Structure
Human p53 is 393 amino acids long and has seven domains:

  • An N-terminal transcription-activation domain (TAD), also known as activation domain 1 (AD1) which activates transcription factors: residues 1-42.
  • An activation domain 2 (AD2) important for apoptotic activity: residues 43-63.
  • A Proline rich domain important for the apoptotic activity of p53: residues 80-94.
  • A central DNA-binding core domain (DBD). Contains one zinc atom and several arginine amino acids: residues 100-300.
  • A nuclear localization signalling domain, residues 316-325.
  • A homo-oligomerisation domain (OD): residues 307-355. Tetramerization is essential for the activity of p53 in vivo.
  • A C-terminal involved in downregulation of DNA binding of the central domain: residues 356-393.

Mutations that deactivate p53 in cancer usually occur in the DBD. Most of these mutations destroy the ability of the protein to bind to its target DNA sequences, and thus prevents transcriptional activation of these genes. As such, mutations in the DBD are recessive loss-of-function mutations. Molecules of p53 with mutations in the OD dimerise with wild-type p53, and prevent them from activating transcription. Therefore OD mutations have a dominant negative effect on the function of p53.

Wild-type p53 is a labile protein, comprising folded and unstructured regions which function in a synergistic manner.

Functional significance

p53 has many anti-cancer mechanisms:

  • It can activate DNA repair proteins when DNA has sustained damage.
  • It can also hold the cell cycle at the G1/S regulation point on DNA damage recognition (if it holds the cell here for long enough, the DNA repair proteins will have time to fix the damage and the cell will be allowed to continue the cell cycle.)
  • It can initiate apoptosis, the programmed cell death, if the DNA damage proves to be irreparable.


p53 is central to many of the cell's anti-cancer mechanisms. It can induce growth arrest, apoptosis and cell senescence. In normal cells p53 is usually inactive, bound to the protein MDM2 (also called HDM2 in humans), which prevents its action and promotes its degradation by acting as ubiquitin ligase. Active p53 is induced after the effects of various cancer-causing agents such as UV radiation, oncogenes and some DNA-damaging drugs. DNA damage is sensed by 'checkpoints' in a cell's cycle, and causes proteins such as ATM, CHK1 and CHK2 to phosphorylate p53 at sites that are close to or within the MDM2-binding region and p300-binding region of the protein. Oncogenes also stimulate p53 activation, mediated by the protein p14ARF. Some oncogenes can also stimulate the transcription of proteins which bind to MDM2 and inhibit its activity. Once activated p53 activates expression of several genes including one encoding for p21. p21 binds to the G1-S/CDK and S/CDK complexes (molecules important for the G1/S transition in the cell cycle) inhibiting their activity. p53 has many anticancer mechanisms, and plays a role in apoptosis, genetic stability, and inhibition of angiogenesis.

The p53 gene has been mapped to chromosome 17. In the cell, p53 protein binds DNA, which in turn stimulates another gene to produce a protein called p21 that interacts with a cell division-stimulating protein (cdk2). When p21 is complexed with cdk2 the cell cannot pass through to the next stage of cell division. Mutant p53 can no longer bind DNA in an effective way, and as a consequence the p21 protein is not made available to act as the 'stop signal' for cell division. Thus cells divide uncontrollably, and form tumors.

Recent research has also linked the p53 and RB1 pathways, via p14ARF, raising the possibility that the pathways may regulate each other.

Research published in 2007 showed when p53 expression is stimulated by sunlight, it begins the chain of events leading to tanning.


Regulation of p53 activity
p53 becomes activated in response to a myriad of stress types, which include but is not limited to DNA damage (induced by either UV, IR or chemical agents,such as hydrogen peroxide), oxidative stress, osmotic shock, ribonucleotide depletion and deregulated oncogene expression. This activation is marked by two major events. Firstly, the half-life of the p53 protein is increased drastically, leading to a quick accumulation of p53 in stressed cells. Secondly, a conformational change forces p53 to take on an active role as a transcription regulator in these cells. The critical event leading to the activation of p53 is the phosphorylation of its N-Terminal domain. The N-Terminal transcriptional activation domain contains a large number of phosphorylation sites and can be considered as the primary target for protein kinases transducing stress signals.

The protein kinases which are known to target this transcriptional activation domain of p53, can roughly be divided into two groups. A first group of protein kinases belongs to the MAPK family (JNK1-3, ERK1-2, p38 MAPK), which is known to respond to several types of stress, such as membrane damage, oxidative stress, osmotic shock, heat shock, etc... A second group of protein kinases (ATR, ATM, Chk1, Chk2, DNA-PK, CAK) is implicated in the genome integrity checkpoint, a molecular cascade that detects and responds to several forms of DNA damage caused by genotoxic stress.

In unstressed cells, p53 levels are kept low through a continuous degradation of p53. A protein called Mdm2 binds to p53 and transports it from the nucleus to the cytosol where it becomes degraded by the proteasome. Phosphorylation of the N-terminal end of p53 by the above mentioned protein kinases disrupts Mdm2-binding. Other proteins, such as Pin1, are then recruited to p53 and induce a conformational change in p53 which prevents Mdm2-binding even more. Trancriptional coactivators, like p300 or PCAF, then acetylate the carboxy-terminal end of p53, exposing the DNA binding domain of p53, allowing it to activate or repress specific genes. Deacetylase enzymes, such as Sirt1 and Sirt7 can deacetylate p53, leading to an inhibition of apoptosis.

Role in disease
If the TP53 gene is damaged, tumor suppression is severely reduced. People who inherit only one functional copy of the TP53 gene will most likely develop tumors in early adulthood, a disease known as Li-Fraumeni syndrome. The TP53 gene can also be damaged in cells by mutagens (chemicals, radiation or viruses), increasing the likelihood that the cell will begin uncontrolled division. More than 50 percent of human tumors contain a mutation or deletion of the TP53 gene. Increasing the amount of p53, which may initially seem a good way to treat tumors or prevent them from spreading, is in actuality not a usable method of treatment, since it can cause premature aging. However, restoring endogenous p53 function holds a lot of promise.

Certain pathogens can also affect the p53 protein that the TP53 gene expresses. One such example, the Human papillomavirus (HPV), encodes a protein, E6, which binds the p53 protein and inactivates it. This, in synergy with the inactivation of another cell cycle regulator, p105RB, allows for repeated cell division manifestested in the clinical disease of warts.

In healthy humans, the p53 protein is continually produced and degraded in the cell. The degradation of the p53 protein is, as mentioned, associated with MDM2 binding. In a negative feedback loop MDM2 is itself induced by the p53 protein. However mutant p53 proteins often don't induce MDM2, and are thus able to accumulate at very high concentrations. Worse, mutant p53 protein itself can inhibit normal p53 protein levels.