PKN3 (gene)
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PKN3 (gene)
PKN3 is a protein kinase C-related molecule and thought to be an effector mediating malignant cell growth downstream of activated phosphoinositide 3-kinase (PI3K). It is thought that chronic activation of the phosphoinositide 3-kinase (PI3K)/ PTEN signal transduction pathway contributes to metastatic cell growth and that PKN3 may mediate that growt1 PKN3 is required for invasive prostate cell growth as assessed by 3D cell culture assays and in an orthotopic mouse tumor model by inducible expression of short hairpin RNA (shRNA). PKN3 may represent a target for therapeutic intervention in cancers that lack tumor suppressor PTEN function or depend on chronic activation of PI3K. Interactions PKN3 (gene) has been shown to interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ... wi ...
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Protein Kinase C
In cell biology, Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins, or a member of this family. PKC enzymes in turn are activated by signals such as increases in the concentration of diacylglycerol (DAG) or calcium ions (Ca2+). Hence PKC enzymes play important roles in several signal transduction cascades. In biochemistry, the PKC family consists of fifteen isozymes in humans. They are divided into three subfamilies, based on their second messenger requirements: conventional (or classical), novel, and atypical. Conventional (c)PKCs contain the isoforms α, βI, βII, and γ. These require Ca2+, DAG, and a phospholipid such as phosphatidylserine for activation. Novel (n)PKCs include the δ, ε, η, and θ isoforms, and require DAG, but do not require Ca2+ for ...
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Effector (biology)
In biochemistry, an effector molecule is usually a small molecule that selectively binds to a protein and regulates its biological activity. In this manner, effector molecules act as ligands that can increase or decrease enzyme activity, gene expression, or cell signaling. Effector molecules can also directly regulate the activity of some mRNA molecules (riboswitches). Other examples of effector functions in biochemistry include hormone signaling and immune response. In some cases, specific proteins serve the same role as effector molecules (note: small molecules refers to organic compounds similar in size to amino acids or RNA strands. Most effector molecules are therefor much smaller than individual proteins, which consist of many amino acids). One example of this is in cellular signal transduction cascades. The term ''effector'' is used in other fields of biology. For instance, the effector end of a neuron is the terminus where an axon makes contact with the muscle or o ...
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Malignant Cell
Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malignancy is not self-limited in its growth, is capable of invading into adjacent tissues, and may be capable of spreading to distant tissues. A benign tumor has none of those properties. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis. Malignant tumors are also characterized by genome instability, so that cancers, as assessed by whole genome sequencing, frequently have between 10,000 and 100,000 mutations in their entire genomes. Cancers usually show tumour heterogeneity, containing multiple subclones. They also frequently have reduced expression of DNA repair enzymes due to Epigenetics#DNA repair epigenetics in cancer, epigenetic methylation of DNA repair genes or altered MicroRNA#DNA repair and cancer, micr ...
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PI3K
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 had ...
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PTEN (gene)
Phosphatase and tensin homolog (PTEN) is a phosphatase in humans and is encoded by the ''PTEN'' gene. Mutations of this gene are a step in the development of many cancers, specifically glioblastoma, lung cancer, breast cancer, and prostate cancer. Genes corresponding to PTEN (orthologs) have been identified in most mammals for which complete genome data are available. ''PTEN'' acts as a tumor suppressor gene through the action of its phosphatase protein product. This phosphatase is involved in the regulation of the cell cycle, preventing cells from growing and dividing too rapidly. It is a target of many anticancer drugs. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin-like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It nega ...
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Signal Transduction Pathway
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellular response. Proteins responsible for detecting stimuli are generally termed receptor (biology), receptors, although in some cases the term sensor is used. The changes elicited by ligand binding (or signal sensing) in a receptor give rise to a biochemical cascade, which is a chain of biochemical events known as a Cell signaling#Signaling pathways, signaling pathway. When signaling pathways interact with one another they form networks, which allow cellular responses to be coordinated, often by combinatorial signaling events. At the molecular level, such responses include changes in the transcription (biology), transcription or translation (biology), translation of genes, and post-translational modification, post-translation ...
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ShRNA
A short hairpin RNA or small hairpin RNA (shRNA/Hairpin Vector) is an artificial RNA molecule with a tight hairpin turn that can be used to silence target gene expression via RNA interference (RNAi). Expression of shRNA in cells is typically accomplished by delivery of plasmids or through viral or bacterial vectors. shRNA is an advantageous mediator of RNAi in that it has a relatively low rate of degradation and turnover. However, it requires use of an expression vector, which has the potential to cause side effects in medicinal applications. The promoter choice is essential to achieve robust shRNA expression. At first, polymerase III promoters such as U6 and H1 were used; however, these promoters lack spatial and temporal control. As such, there has been a shift to using polymerase II promoters, which are inducible, to regulate shRNA expression. Delivery Expression of shRNA in cells can be obtained by delivery of plasmids or through viral or bacterial vectors. Delivery of ...
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ARHGAP26
Rho GTPase activating protein 26 (ARHGAP26) also known as GTPase Regulator Associated with Focal Adhesion Kinase (GRAF) is a protein that in humans is encoded by the ''ARHGAP26'' gene. Function GRAF1 is a multidomain protein that is necessary for the CLIC/ GEEC endocytic pathway. By virtue of an N-terminal BAR domain, GRAF1 sculpts the endocytic membranes of this pathway into 40 nm diameter tubules and vesicles that allow uptake of extracellular fluid, GPI-linked proteins and certain bacterial exotoxins into cells. The role of dynamin in the CLIC/GEEC pathway is controversial, but GRAF1 interacts strongly with this protein and acute inhibition of dynamin action abrogates CLIC/GEEC endocytosis. There are several members of the GRAF family of proteins, including GRAF2, GRAF3, and oligophrenin, all of which likely playing similar roles during clathrin-independent endocytic events. Mutations of both GRAF1 and oligophrenin are strongly implicated in causing human disease ( ...
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