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GTP-binding protein Di-Ras3 (DIRAS3) also known as aplysia ras homology member I (ARHI) is a protein that in humans is encoded by the DIRAS3 gene. This gene is a member of the Ras superfamily and is expressed in normal ovarian and breast epithelial cells but not in ovarian and breast cancers. It is a maternally imprinted gene, with monoallelic expression of the paternal allele, which is associated with growth suppression. Thus, this gene appears to be a putative tumor suppressor gene whose function is abrogated in ovarian and breast cancers. DIRAS3 is linked to breast cancer as well as ovarian cancer. The ''DIRAS3'' gene includes one promoter, two exons and one intron with a 687 bp protein-coding region that encodes a 26-kDa protein. The DIRAS3 protein is a GTPase belonging to the Ras superfamily and shares 50–60% homology with Ras and Rap, two other small GTP binding proteins. Reduced expression of DIRAS3 has been reported in 70% of invasive breast cancers. Structure and ...
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Genomic Imprinting
Genomic imprinting is an epigenetic phenomenon that causes genes to be expressed or not, depending on whether they are inherited from the female or male parent. Genes can also be partially imprinted. Partial imprinting occurs when alleles from both parents are differently expressed rather than complete expression and complete suppression of one parent's allele. Forms of genomic imprinting have been demonstrated in fungi, plants and animals. In 2014, there were about 150 imprinted genes known in mice and about half that in humans. As of 2019, 260 imprinted genes have been reported in mice and 228 in humans. Genomic imprinting is an inheritance process independent of the classical Mendelian inheritance. It is an epigenetic process that involves DNA methylation and histone methylation without altering the genetic sequence. These epigenetic marks are established ("imprinted") in the germline (sperm or egg cells) of the parents and are maintained through mitotic cell divisions in the ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metabolic reactions, DNA replication, Cell signaling, responding to stimuli, providing Cytoskeleton, structure to cells and Fibrous protein, organisms, and Intracellular transport, transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the Nucleic acid sequence, nucleotide sequence of their genes, and which usually results in protein folding into a specific Protein structure, 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called pep ...
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Amino Acid Residue
In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of electrons. Amines can also exist as hetero cyclic compounds. Aniline is the simplest aromatic amine, consisting of a benzene ring bonded to an amino group. Amines are classified into three types: primary (1°), secondary (2°), and tertiary (3°) amines. Primary amines (1°) contain one alkyl or aryl substituent and have the general formula RNH2. Secondary amines (2°) have two alkyl or aryl groups attached to the nitrogen atom, with the general formula R2NH. Tertiary amines (3°) contain three substituent groups bonded to the nitrogen atom, and are represented by the formula R3N. The functional group present in primary amines is called the amino group. Classification of amines Amines can be classified according to the nature and number ...
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Knudson Hypothesis
The two-hit hypothesis, also known as the Knudson hypothesis, is the hypothesis that most tumor suppressor genes require both alleles to be inactivated, either through mutations or through epigenetic silencing, to cause a phenotypic change. It was first formulated by Alfred G. Knudson in 1971 and led indirectly to the identification of tumor suppressor genes. Knudson won the 1998 Albert Lasker Clinical Medical Research Award for this work. Knudson performed a statistical analysis on cases of retinoblastoma, a malignant tumor of the retina that occurs both as an inherited disease and sporadically. He noted that inherited retinoblastoma occurs at a younger age than the sporadic disease. In addition, the children with inherited retinoblastoma often developed the tumor in both eyes, suggesting an underlying predisposition. Knudson suggested that two "hits" to DNA were necessary to cause the cancer. In the children with inherited retinoblastoma, the first mutation in what later ca ...
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MAPK/ERK Pathway
The MAPK/ERK pathway (also known as the Ras-Raf-MEK-ERK pathway) is a chain of proteins in the cell (biology), cell that communicates a signal from a Receptor (biochemistry), receptor on the surface of the cell to the DNA in the nucleus of the cell. The signal starts when a signaling molecule binds to the receptor on the cell surface and ends when the DNA in the nucleus expresses a protein and produces some change in the cell, such as cell division. The pathway includes many proteins, such as mitogen-activated protein kinases (MAPKs), originally called extracellular signal-regulated kinases (ERKs), which communicate by adding phosphate groups to a neighboring protein (Phosphorylation, phosphorylating it), thereby acting as an "on" or "off" switch. When one of the proteins in the pathway is mutated, it can become stuck in the "on" or "off" position, a necessary step in the development of many cancers. In fact, components of the MAPK/ERK pathway were first discovered in cancer cells ...
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Downregulated
In biochemistry, in the biological context of organisms' regulation of gene expression and production of gene products, downregulation is the process by which a cell decreases the production and quantities of its cellular components, such as RNA and proteins, in response to an external stimulus. The complementary process that involves increase in quantities of cellular components is called upregulation. An example of downregulation is the cellular decrease in the expression of a specific receptor in response to its increased activation by a molecule, such as a hormone or neurotransmitter, which reduces the cell's sensitivity to the molecule. This is an example of a locally acting (negative feedback) mechanism. An example of upregulation is the response of liver cells exposed to such xenobiotic molecules as dioxin. In this situation, the cells increase their production of cytochrome P450 enzymes, which in turn increases degradation of these dioxin molecules. Downregulation or upr ...
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Upregulated
In biochemistry, in the biological context of organisms' regulation of gene expression and production of gene products, downregulation is the process by which a cell decreases the production and quantities of its cellular components, such as RNA and proteins, in response to an external stimulus. The complementary process that involves increase in quantities of cellular components is called upregulation. An example of downregulation is the cellular decrease in the expression of a specific receptor in response to its increased activation by a molecule, such as a hormone or neurotransmitter, which reduces the cell's sensitivity to the molecule. This is an example of a locally acting (negative feedback) mechanism. An example of upregulation is the response of liver cells exposed to such xenobiotic molecules as dioxin. In this situation, the cells increase their production of cytochrome P450 enzymes, which in turn increases degradation of these dioxin molecules. Downregulation or ...
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Cyclin D1
Cyclin D1 is a protein that in humans is encoded by the ''CCND1'' gene. Gene expression The CCND1 gene encodes the cyclin D1 protein. The human CCND1 gene is located on the long arm of chromosome 11 (band 11q13). It is 13,388 base pairs long, and translates into 295 amino acids. Cyclin D1 is expressed in all adult human tissues with the exception of cells derived from bone marrow stem cell lines (both lymphoid and myeloid). Protein structure Cyclin D1 is composed of the following protein domains and motifs: * retinoblastoma protein (pRb) binding motif; * cyclin box domain for cyclin-dependent kinase (CDK) binding and CDK inhibitor binding; * LxxLL binding motif for co-activator recruitment; * PEST sequence that may mark the protein for degradation; * threonine residue (threonine 286) that controls nuclear export and protein stability. Function The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic ...
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Epithelial Cells
Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of many internal organs, the corresponding inner surfaces of body cavities, and the inner surfaces of blood vessels. Epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. These tissues also lack blood or lymph supply. The tissue is supplied by nerves. There are three principal shapes of epithelial cell: squamous (scaly), columnar, and cuboidal. These can be arranged in a singular layer of cells as simple epithelium, either simple squamous, simple columnar, or simple cuboidal, or in layers of two or more cells deep as stratified (layered), or ''compound'', either squamous, columnar or cuboidal. In some tissues, a layer of columnar cells may appear to be stratified due ...
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Lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group (which is in the deprotonated form when the lysine is dissolved in water at physiological pH), and a side chain (which is partially protonated when the lysine is dissolved in water at physiological pH), and so it is classified as a basic, charged (in water at physiological pH), aliphatic amino acid. It is encoded by the codons AAA and AAG. Like almost all other amino acids, the α-carbon is chiral and lysine may refer to either enantiomer or a racemic mixture of both. For the purpose of this article, lysine will refer to the biologically active enantiomer L-lysine, where the α-carbon is in the ''S'' configuration. The human body cannot synthesize lysine. It is essential in humans and must therefore be obtained from the diet. In orga ...
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Glutamine
Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral, polar amino acid. It is non-essential and conditionally essential in humans, meaning the body can usually synthesize sufficient amounts of it, but in some instances of stress, the body's demand for glutamine increases, and glutamine must be obtained from the diet. It is encoded by the codons CAA and CAG. It is named after glutamic acid, which in turn is named after its discovery in cereal proteins, gluten. In human blood, glutamine is the most abundant free amino acid. The dietary sources of glutamine include especially the protein-rich foods like beef, chicken, fish, dairy products, eggs, vegetables like beans, beets, cabbage, spinach, carrots, parsley, vegetable juices and also in wheat, papaya, Brussels sprouts, celery, kale ...
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Alanine
Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group side chain. Consequently it is classified as a non-polar, aliphatic α-amino acid. Under biological conditions, it exists in its zwitterionic form with its amine group protonated (as ) and its carboxyl group deprotonated (as ). It is non-essential to humans as it can be synthesized metabolically and does not need to be present in the diet. It is encoded by all codons starting with G C (GC U, GCC, GC A, and GCG). The L-isomer of alanine (left-handed) is the one that is incorporated into proteins. L-alanine is second only to L-leucine in rate of occurrence, accounting for 7.8% of the primary structure in a sample of 1,150 proteins. The right-handed form, D-alanine, occurs in peptides in some bacterial cell walls (in peptidoglycan) ...
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