Tumor suppresor involved in HPV - yelito61

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Cancer

HPV-induced cancersAbout a dozen HPV types (including types 16, 18, 31 and 45) are called "high-risk" types because they can cause cervical cancer, as well as anal cancer, vulvar cancer, head and neck cancers, and penile cancer (Parkin 2006). HPV-induced cancers often have viral sequences integrated into the cellular DNA. Some of the HPV "early" genes, such as E6 and E7, are known to act as oncogenes that promote tumor growth and malignant transformation.

The p53 protein prevents cell growth in the presence of DNA damage primarily through the BAX domain, which blocks the anti-apoptotic effects of the mitochondrial BCL-2 receptor. In addition, p53 also upregulates the p21 protein, which blocks the formation of the Cyclin D/Cdk4 complex, thereby preventing the phosphorylation of RB and, in turn, halting cell cycle progression by preventing the activation of E2F. In short, p53 is a tumor suppressor gene that arrests the cell cycle when there is DNA damage. The E6 and E7 proteins work by inhibiting tumor suppression genes involved in that pathway: E6 inhibits p53, while E7 inhibits p53, p21, and RB.

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thank for the explanation on the important subject.

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A homeobox is a DNA sequence found within genes that are involved in the regulation of development (morphogenesis) of animals, fungi and plants. Genes that have a homeobox are called homeobox genes and form the homeobox gene family. They were discovered independently in 1983 by Walter Gehring and his colleagues at the University of Basel, Switzerland, and Matthew Scott and Amy Weiner, who were then working with Thomas Kaufman at Indiana University in Bloomington.

A homeobox is about 180 base pairs long; it encodes a protein domain (the homeodomain) which can bind DNA. Homeobox genes encode transcription factors which typically switch on cascades of other genes, for instance all the ones needed to make a leg. The homeodomain binds DNA in a specific manner. However, the specificity of a single homeodomain protein is usually not enough to recognize only its desired target genes. Most of the time, homeodomain proteins act in the promoter region of their target genes as complexes with other transcription factors, often also homeodomain proteins. Such complexes have a much higher target specificity than a single homeodomain protein.

A particular subgroup of homeobox genes are the Hox genes, which are found in a special gene cluster, the Hox cluster (also called Hox complex). Hox genes function in patterning the body axis. Thus, by providing the identity of particular body regions, Hox genes determine where limbs and other body segments will grow in a developing fetus or larva. Mutations in any one of these genes can lead to the growth of extra, typically non-functional body parts in invertebrates, for example antennapedia complex in Drosophila, which results in a leg growing from the head in place of an antenna and is due to a defect in a single gene (this mutation is also known as Antennapedia). Mutation in vertebrate Hox genes usually results in spontaneous abortion.

The homeobox genes were first found in the fruit fly Drosophila melanogaster and have subsequently been identified in many other species, from insects to reptiles and mammals. The diagram to the right is a structural model of the Rattus norvegicus Pit-1 homeobox-containing protein (purple) bound to DNA. Pit-1 is a regulator of growth hormone gene transcription. Pit-1 is a member of the POU DNA-binding domain family of transcription factors so it can bind to DNA using both the POU domain and the homeodomain. Homeobox genes have even been found in fungi, for example the one-cellular yeasts, and plants. The well known homeotic genes in plants (MADS-box genes) are not homologous to Hox genes in animals. Plants and animals do not share the same homeotic genes, and this suggests that homeotic genes arose once in the early evolution of animals and once again in the early evolution of plants. Humans generally contain homeobox genes in four clusters, called HOXA (or sometimes HOX1), HOXB, HOXC, or HOXD, on chromosomes 7, 17, 12, and 2, respectively.

Mutations to homeobox genes can produce easily visible phenotypic changes. Two examples of homeobox mutations in the above-mentioned fruit fly are legs where the antennae should be, and a second pair of wings. Duplication of homeobox genes can produce new body segments, and such duplications are likely to have been important in the evolution of segmented animals. Interestingly, there is one insect family, the xyelid sawflies, in which both the antennae and mouthparts are remarkably leg-like in structure.


Above some characteristics of Hox genes.

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DNA gyrase :

DNA gyrase, often referred to simply as gyrase, is a type II topoisomerase (EC 5.99.1.3) that introduces negative supercoils (or relaxes positive supercoils) into DNA by looping the template so as to form a crossing, then cutting one of the double helices and passing the other through it before resealing the break, changing the linking number by two in each enzymatic step.

The unique ability of gyrase to introduce negative supercoils into DNA is what allows bacterial DNA to have free negative supercoils. The ability of gyrase to relax positive supercoils comes into play during DNA replication. The right-handed nature of the DNA double helix causes positive supercoils to accumulate ahead of a translocating enzyme, in the case of DNA replication, a DNA polymerase. The ability of gyrase (and topoisomerase IV) to relax positive supercoils allows superhelical tension ahead of the polymerase to be released so that replication can continue

Above the function of DNA Gyrase.

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How Aspirin and NSAIDs Work:

Prostaglandins and NSAIDS
Prostaglandins are potent mediators of inflammation. The first and committed step in the production of prostaglandins from arachidonic acid is the bis-oxygenation of arachindonate to prostaglandin PGG2. This is followed by reduction to PGH2 in a peroxidase reaction. Both these reactions are catalyzed by cyclooxygenase, also known as PGH synthase.

Cyclooxygenase (COX) is inhibited by the family of drugs known as non-steroidal anti-inflammatory drugs or NSAIDs. Aspirin, ibuprofen, flurbiprofen and acetaminophen (trade name Tylenol) are all NSAIDs.

There are two isoforms of COX in animals: COX-1, which carries out normal, physiological production of prostaglandins, and COX-2, which is induced by cytokines, mitogens and endotoxins in inflammatory cells, and which is responsible for the production of prostaglandins in inflammation.

Above the mechanism of Aspirin and NSAIDs.

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Aspirin's ability to suppress the production of prostaglandins and thromboxanes is due to its non-competitive and irreversible inhibition of the cyclooxygenase (COX) enzyme. Cyclooxygenase is required for prostaglandin and thromboxane synthesis. Aspirin acts as an acetylating agent where an acetyl group is covalently attached to a serine residue in the active site of the COX enzyme. This makes aspirin different from other NSAIDs (such as diclofenac and ibuprofen), which are reversible inhibitors( inhibit COX for 48 hours).

More about Aspirin.

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Aspirin, is analgesic, anti-inflammatory, antipyretic and is an inhibitor of platelet aggregation. It inhibits fatty acid cyclo-oxygenase by acetylation of the active site of enzyme and the pharmacological effects of aspirin are due to the inhibition of the formation of cyclo-oxygenase products including prostglandins, thromboxanes and prostacyclin.

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Brachial plexux injury:


The brachial plexus is responsible for cutaneous and muscular innervation of the entire upper limb, with two exceptions: the trapezius muscle innervated by the spinal accessory nerve and an area of skin near the axilla innervated by the intercostobrachialis nerve.

Therefore, lesions of the plexus can lead to severe functional impairment.



Pathway:
One can remember the order of brachial plexus elements by way of the mnemonic, "Randy Travis Drinks Cold Beer" - Roots, Trunks, Divisions, Cords, Branches[1]

The five roots are the five anterior rami of the spinal nerves, after they have given off their segmental supply to the muscles of the neck.
These roots merge to form three trunks:
"superior"[2] or "upper" (C5-C6)
"middle"[3] (C7)
"inferior"[4] or "lower" (C8-T1)
Each trunk then splits in two, to form six divisions:
anterior division[5] of the superior, middle, and inferior trunks
posterior division[6] of the superior, middle, and inferior trunks
These six divisions will regroup to become the three cords. The cords are named by their position in respect to the axillary artery.
The posterior cord is formed from the three posterior divisions of the trunks (C5-T1)
The lateral cord is the anterior divisions from the upper and middle trunks (C5-C7)
The medial cord is simply a continuation of the lower trunk (C8-T1)
The branches are listed below. Most branch off of the cords, but a few branch directly off of earlier structures.

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thanks for posting the important information!

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thanks thanks thanks yelito61