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Restriction Point
The restriction point (R), also known as the Start or G1/S checkpoint, is a cell cycle checkpoint in the G1 phase, G1 phase of the animal cell cycle at which the cell becomes "committed" to the cell cycle, and after which extracellular cell signaling, signals are no longer required to stimulate proliferation. The defining biochemical feature of the restriction point is the activation of G1/S- and S-phase Cyclin-dependent kinase complex, cyclin-CDK complexes, which in turn protein phosphorylation, phosphorylate proteins that initiate DNA replication, centrosome duplication, and other early cell cycle events. It is one of three main cell cycle checkpoints, the other two being the G2-M DNA damage checkpoint and the spindle checkpoint. History Originally, Howard Martin Temin showed that chicken cells reach a point at which they are committed to replicate their DNA and are not dependent on extracellular signals. About 20 years later, in 1973, Arthur Pardee demonstrated that a single ...
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Cell Cycle 2-2
Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery with only a few monks or nuns * Prison cell, a room used to hold people in prisons Groups of people * Cell, a group of people in a cell group, a form of Christian church organization * Cell, a unit of a clandestine cell system, a penetration-resistant form of a secret or outlawed organization * Cellular organizational structure, such as in business management Science, mathematics, and technology Computing and telecommunications * Cell (EDA), a term used in an electronic circuit design schematics * Cell (microprocessor), a microprocessor architecture developed by Sony, Toshiba, and IBM * Memory cell (computing), the basic unit of (volatile or non-volatile) computer memory * Cell, a unit in a database table or spreadsheet, formed by ...
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Epidermal Growth Factor
Epidermal growth factor (EGF) is a protein that stimulates cell growth and differentiation by binding to its receptor, EGFR. Human EGF is 6-k Da and has 53 amino acid residues and three intramolecular disulfide bonds. EGF was originally described as a secreted peptide found in the submaxillary glands of mice and in human urine. EGF has since been found in many human tissues, including platelets, submandibular gland (submaxillary gland), and parotid gland. Initially, human EGF was known as urogastrone. Structure In humans, EGF has 53 amino acids (sequence NSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCQYRDLKWWELR), with a molecular mass of around 6 kDa. It contains three disulfide bridges (Cys6-Cys20, Cys14-Cys31, Cys33-Cys42). Function EGF, via binding to its cognate receptor, results in cellular proliferation, differentiation, and survival. Salivary EGF, which seems to be regulated by dietary inorganic iodine, also plays an important physiological role in the mai ...
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Protein Kinase B
Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases that play key roles in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, and cell migration. Family members - Isoforms There are three different genes that encode isoforms of Protein kinase B. These three genes are referred to as AKT1, AKT2, and AKT3 and encode the RAC alpha, beta, and gamma serine/threonine protein kinases respectively. The terms PKB and Akt may refer to the products of all three genes collectively, but sometimes are used to refer to PKB alpha and Akt1 alone. Akt1 is involved in cellular survival pathways, by inhibiting apoptotic processes. Akt1 is also able to induce protein synthesis pathways, and is therefore a key signaling protein in the cellular pathways that lead to skeletal muscle hypertrophy and general tissue growth. A mouse model with complete deletion of the Akt1 g ...
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Phosphoinositide 3-kinase
Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. PI3Ks are a family of related intracellular signal transducer enzymes capable of phosphorylating the 3 position hydroxyl group of the inositol ring of phosphatidylinositol (PtdIns). The pathway, with oncogene PIK3CA and tumor suppressor gene PTEN, is implicated in the sensitivity of cancer tumors to insulin and IGF1, and in calorie restriction. Discovery The discovery of PI3Ks by Lewis Cantley and colleagues began with their identification of a previously unknown phosphoinositide kinase associated with the polyoma middle T protein. They observed unique substrate specificity and chromatographic properties of the products of the lipid kinase, leading to the discovery that this phosphoinositide kinase ha ...
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Cyclin-dependent Kinase 2
Cyclin-dependent kinase 2, also known as cell division protein kinase 2, or Cdk2, is an enzyme that in humans is encoded by the ''CDK2'' gene. The protein encoded by this gene is a member of the cyclin-dependent kinase family of Ser/Thr protein kinases. This protein kinase is highly similar to the gene products of ''S. cerevisiae'' cdc28, and '' S. pombe'' cdc2, also known as Cdk1 in humans. It is a catalytic subunit of the cyclin-dependent kinase complex, whose activity is restricted to the G1-S phase of the cell cycle, where cells make proteins necessary for mitosis and replicate their DNA. This protein associates with and is regulated by the regulatory subunits of the complex including cyclin E or A. Cyclin E binds G1 phase Cdk2, which is required for the transition from G1 to S phase while binding with Cyclin A is required to progress through the S phase. Its activity is also regulated by phosphorylation. Multiple alternatively spliced variants and multiple transcription in ...
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Cyclin-dependent Kinase 4
Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the ''CDK4'' gene. CDK4 is a member of the cyclin-dependent kinase family. Function The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of '' S. cerevisiae'' cdc28 and ''S. pombe'' cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16INK4a. This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product ( Rb). Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition. Phosphorylation of RB1 allows dissoci ...
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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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AP-1 Transcription Factor
Activator protein 1 (AP-1) is a transcription factor that regulates gene expression in response to a variety of stimuli, including cytokines, growth factors, stress, and bacterial and viral infections. AP-1 controls a number of cellular processes including differentiation, proliferation, and apoptosis. The structure of AP-1 is a heterodimer composed of proteins belonging to the c-Fos, c-Jun, ATF and JDP families. History AP-1 was first discovered as a TPA-activated transcription factor that bound to a cis-regulatory element of the human metallothionein IIa ( hMTIIa) promoter and SV40. The AP-1 binding site was identified as the 12-O-Tetradecanoylphorbol-13-acetate ( TPA) response element (TRE) with the consensus sequence 5’-TGA G/C TCA-3’. The AP-1 subunit Jun was identified as a novel oncoprotein of avian sarcoma virus, and Fos-associated p39 protein was identified as the transcript of the cellular Jun gene. Fos was first isolated as the cellular homologu ...
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C-Fos
Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the ''FOS'' gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV (Finkel–Biskis–Jinkins murine osteogenic sarcoma virus) (Curran and Tech, 1982). It is a part of a bigger Fos family of transcription factors which includes c-Fos, FosB, Fra-1 and Fra-2. It has been mapped to chromosome region 14q21→q31. c-Fos encodes a 62 kDa protein, which forms heterodimer with c-jun (part of Jun family of transcription factors), resulting in the formation of AP-1 (Activator Protein-1) complex which binds DNA at AP-1 specific sites at the promoter and enhancer regions of target genes and converts extracellular signals into changes of gene expression. It plays an important role in many cellular functions and has been found to be overexpressed in a variety of cancers. Structure and function c-Fos is a 380 amino acid protein with a bas ...
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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 that communicates a signal from a 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 ( 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, and drugs that reverse the "on" or "off" switch are ...
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Mitogen-activated Protein Kinase
A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine and threonine (i.e., a serine/threonine-specific protein kinase). MAPKs are involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflammatory cytokines. They regulate cell functions including proliferation, gene expression, differentiation, mitosis, cell survival, and apoptosis. MAP kinases are found in eukaryotes only, but they are fairly diverse and encountered in all animals, fungi and plants, and even in an array of unicellular eukaryotes. MAPKs belong to the CMGC (CDK/MAPK/GSK3/CLK) kinase group. The closest relatives of MAPKs are the cyclin-dependent kinases (CDKs). Discovery The first mitogen-activated protein kinase to be discovered was ERK1 ( MAPK3) in mammals. Since ERK1 and its close relative ERK2 ( MAPK1) are both involved in growth factor signaling, the family ...
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Ras Subfamily
Ras, from "Rat sarcoma virus", is a family of related proteins that are expressed in all animal cell lineages and organs. All Ras protein family members belong to a class of protein called small GTPase, and are involved in transmitting signals within cells ( cellular signal transduction). Ras is the prototypical member of the Ras superfamily of proteins, which are all related in three-dimensional structure and regulate diverse cell behaviours. When Ras is 'switched on' by incoming signals, it subsequently switches on other proteins, which ultimately turn on genes involved in cell growth, differentiation, and survival. Mutations in Ras genes can lead to the production of permanently activated Ras proteins, which can cause unintended and overactive signaling inside the cell, even in the absence of incoming signals. Because these signals result in cell growth and division, overactive Ras signaling can ultimately lead to cancer. The three Ras genes in humans ('' HRAS'', ''KRAS'' ...
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