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YAP1
YAP1 (yes-associated protein 1), also known as YAP or YAP65, is a protein that acts as a transcription coregulator that promotes transcription of genes involved in cellular proliferation and suppressing apoptotic genes. YAP1 is a component in the hippo signaling pathway which regulates organ size, regeneration, and tumorigenesis. YAP1 was first identified by virtue of its ability to associate with the SH3 domain of Yes and Src protein tyrosine kinases. ''YAP1'' is a potent oncogene, which is amplified in various human cancers. Structure Cloning of the YAP1 gene facilitated the identification of a modular protein domain, known as the WW domain. Two splice isoforms of the YAP1 gene product were initially identified, named YAP1-1 and YAP1-2, which differed by the presence of an extra 38 amino acids that encoded the WW domain. Apart from the WW domain, the modular structure of YAP1 contains a proline-rich region at the very amino terminus, which is followed by a TID (TEA ...
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WW Domain
The WW domain (also known as the rsp5-domain or WWP repeating structural motif, motif) is a modular protein domain that mediates specific interactions with protein ligands. This domain is found in a number of unrelated signaling and structural proteins and may be repeated up to four times in some proteins. Apart from binding preferentially to proteins that are proline-rich, with particular proline-motifs, [AP]-P-P-[AP]-Y, some WW domains bind to phosphoserine- and phosphothreonine-containing motifs. Structure and ligands The WW domain is one of the smallest protein modules, composed of only 40 amino acids, which mediates specific protein-protein interactions with short proline-rich or proline-containing motifs. Named after the presence of two conserved tryptophans (W), which are spaced 20-22 amino acids apart within the sequence, the WW domain folds into a meandering triple-stranded beta sheet. The identification of the WW domain was facilitated by the analysis of two splice ...
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Transcription Coregulator
In molecular biology and genetics, transcription coregulators are proteins that interact with transcription factors to either activate or repress the transcription of specific genes. Transcription coregulators that activate gene transcription are referred to as coactivators while those that repress are known as corepressors. The mechanism of action of transcription coregulators is to modify chromatin structure and thereby make the associated DNA more or less accessible to transcription. In humans several dozen to several hundred coregulators are known, depending on the level of confidence with which the characterisation of a protein as a coregulator can be made. One class of transcription coregulators modifies chromatin structure through covalent modification of histones. A second ATP dependent class modifies the conformation of chromatin. Histone acetyltransferases Nuclear DNA is normally tightly wrapped around histones rendering the DNA inaccessible to the general transc ...
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Oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.Kimball's Biology Pages.
"Oncogenes" Free full text
Most normal cells undergo a preprogrammed rapid cell death () if critical functions are altered and then malfunction. Activated oncogenes can cause those cells designated for apoptosis to survive and proliferate instead. Most oncogenes began as proto-oncogenes: normal genes involved in cell growth and proliferation or inhibition of apoptosis. If, through mutation, normal genes promoting cellular growth are up-regulated (gain-of-function mutation), they predispose the cel ...
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Hippo Signaling Pathway
The Hippo signaling pathway, also known as the Salvador-Warts-Hippo (SWH) pathway, is a signaling pathway that controls organ size in animals through the regulation of cell proliferation and apoptosis. The pathway takes its name from one of its key signaling components—the protein kinase Hippo (Hpo). Mutations in this gene lead to tissue overgrowth, or a " hippopotamus"-like phenotype. A fundamental question in developmental biology is how an organ knows to stop growing after reaching a particular size. Organ growth relies on several processes occurring at the cellular level, including cell division and programmed cell death (or apoptosis). The Hippo signaling pathway is involved in restraining cell proliferation and promoting apoptosis. As many cancers are marked by unchecked cell division, this signaling pathway has become increasingly significant in the study of human cancer. The Hippo pathway also has a critical role in stem cell and tissue specific progenitor cell se ...
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SH3 Domain
The SRC Homology 3 Domain (or SH3 domain) is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of phospholipase and several cytoplasmic tyrosine kinases such as Abl and Src. It has also been identified in several other protein families such as: PI3 Kinase, Ras GTPase-activating protein, CDC24 and cdc25. SH3 domains are found in proteins of signaling pathways regulating the cytoskeleton, the Ras protein, and the Src kinase and many others. The SH3 proteins interact with adaptor proteins and tyrosine kinases. Interacting with tyrosine kinases, SH3 proteins usually bind far away from the active site. Approximately 300 SH3 domains are found in proteins encoded in the human genome. In addition to that, the SH3 domain was responsible for controlling protein-protein interactions in the signal transduction pathways and regulating the ...
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Transcription Factors
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The function of TFs is to regulate—turn on and off—genes in order to make sure that they are expressed in the desired cells at the right time and in the right amount throughout the life of the cell and the organism. Groups of TFs function in a coordinated fashion to direct cell division, cell growth, and cell death throughout life; cell migration and organization (body plan) during embryonic development; and intermittently in response to signals from outside the cell, such as a hormone. There are approximately 1600 TFs in the human genome. Transcription factors are members of the proteome as well as regulome. TFs work alone or with other proteins in a complex, by promoting (as an activator), or blocking (as a repressor) the recruitment o ...
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SMAD (protein)
Smads (or SMADs) comprise a family of structurally similar proteins that are the main signal transducers for receptors of the transforming growth factor beta (TGF-B) superfamily, which are critically important for regulating cell development and growth. The abbreviation refers to the homologies to the ''Caenorhabditis elegans'' SMA ("small" worm phenotype) and Mothers against decapentaplegic, MAD family ("Mothers Against Decapentaplegic") of genes in ''Drosophila''. There are three distinct sub-types of Smads: receptor-regulated Smads (R-SMAD, R-Smads), common partner Smads (Co-Smads), and inhibitory Smads (I-SMAD, I-Smads). The eight members of the Smad family are divided among these three groups. Protein trimer, Trimers of two receptor-regulated SMADs and one co-SMAD act as transcription factors that regulate the expression of certain genes. Sub-types The R-Smads consist of mothers against decapentaplegic homolog 1, Smad1, mothers against decapentaplegic homolog 2, Smad2, mothers ...
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TP53BP2
Apoptosis-stimulating of p53 protein 2 (ASPP2) also known as Bcl2-binding protein (Bbp) and tumor suppressor p53-binding protein 2 (p53BP2) is a protein that in humans is encoded by the ''TP53BP2'' gene. Multiple transcript variants encoding different isoforms have been found for this gene. Nomenclature ASPP2 (amino acid residues 600 –1128) was initially identified as 53BP2 (p53-binding protein 2) in a yeast two hybrid screen using p53 as the bait. Another yeast two hybrid screening in which Bcl-2 was used as the bait gave rise to the discovery of another fragment of ASPP2 (residues 123-1128) and it was called Bbp. The full length ASPP2 (1128 amino acids) was identified later. Function ASPP2 plays a central role in regulation of apoptosis and cell growth via its interactions. ASPP2 regulates TP53 by enhancing the DNA binding and transactivation function of TP53 on the Promoter (biology), promoters of proapoptotic genes ''in vivo''. ASPP2 binds to wild-type p53 but fails to ...
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LATS2
Large tumor suppressor kinase 2 (LATS2) is an enzyme that in humans is encoded by the ''LATS2'' gene. This gene encodes a serine/threonine protein kinase belonging to the LATS tumor suppressor family and participates in the Hippo signaling pathway where it inactivates the effector proteins, YAP (protein), YAP and WWTR1, WWTR1 (TAZ). The protein localizes to centrosomes during interphase and early and late metaphase. It interacts with the centrosomal proteins Aurora A kinase, aurora-A and JUB (gene), ajuba and is required for accumulation of Tubulin#γ-Tubulin, gamma-tubulin and spindle apparatus, spindle formation at the onset of mitosis. It also interacts with a negative regulator of p53 and may function in a positive feedback loop with p53 that responds to cytoskeleton damage. Additionally, it can function as a corepressor of Hormone response element, androgen-responsive gene expression. References Further reading

* * * * * * * * * * * * * EC 2.7.11 {{gene-13-stub ...
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LATS1
Large tumor suppressor kinase 1 (LATS1) is an enzyme that in humans is encoded by the ''LATS1'' gene. It has been associated with the Hippo signaling pathway, where it phosphorylates YAP and TAZ to inactivate their function. The protein encoded by this gene is a putative serine/threonine kinase that localizes to the mitotic apparatus and complexes with cell cycle controller CDC2 kinase in early mitosis. The protein is phosphorylated in a cell-cycle dependent manner, with late prophase phosphorylation remaining through metaphase. The N-terminal region of the protein binds CDC2 to form a complex showing reduced histone H1 kinase activity, indicating a role as a negative regulator of CDC2/cyclin A. In addition, the C-terminal kinase domain binds to its own N-terminal region, suggesting potential negative regulation through interference with complex formation via intramolecular binding. Biochemical and genetic data suggest a role as a tumor suppressor. This is supported by stud ...
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PDZ Domain
The PDZ domain is a common structural domain of 80-90 Amino acid, amino-acids found in the Signal transduction, signaling proteins of bacteria, yeast, plants, viruses and animals. Proteins containing PDZ domains play a key role in anchoring receptor proteins in the membrane to cytoskeletal components. Proteins with these domains help hold together and organize signaling complexes at cellular membranes. These domains play a key role in the formation and function of signal transduction complexes. PDZ domains also play a highly significant role in the anchoring of cell surface receptors (such as Cftr and FZD7) to the actin cytoskeleton via mediators like NHERF and ezrin. ''PDZ'' is an initialism combining the first letters of the first three proteins discovered to share the domain — DLG4, post synaptic density protein (PSD95), DLG1, Drosophila disc large tumor suppressor (Dlg1), and Tight junction protein 1, zonula occludens-1 protein (zo-1). PDZ domains have previously been referr ...
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