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SMAD3
Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene. SMAD3 is a member of the SMAD family of proteins. It acts as a mediator of the signals initiated by the transforming growth factor beta (TGF-β) superfamily of cytokines, which regulate cell proliferation, differentiation and death. Based on its essential role in TGF beta signaling pathway, SMAD3 has been related with tumor growth in cancer development. Gene The human SMAD3 gene is located on chromosome 15 on the cytogenic band at 15q22.33. The gene is composed of 9 exons over 129,339 base pairs. It is one of several human homologues of a gene that was originally discovered in the fruit fly ''Drosophila melanogaster''. The expression of SMAD3 has been related to the mitogen-activated protein kinase (MAPK/ERK pathway), particularly to the activity of mitogen-activated protein kinase kinase-1 (MEK1). Studies have demonstrated that inhi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TGF Beta Signaling Pathway
The transforming growth factor beta (TGFB) signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiation, cell migration, apoptosis, cellular homeostasis and other cellular functions. The TGFB signaling pathways are conserved. In spite of the wide range of cellular processes that the TGFβ signaling pathway regulates, the process is relatively simple. TGFβ superfamily ligands bind to a type II receptor, which recruits and phosphorylates a type I receptor. The type I receptor then phosphorylates receptor-regulated SMADs ( R-SMADs) which can now bind the coSMAD SMAD4. R-SMAD/coSMAD complexes accumulate in the nucleus where they act as transcription factors and participate in the regulation of target gene expression. Mechanism Ligand binding The TGF beta superfamily of ligands includes: Bone morphogenetic proteins (BMPs), Growth and differentiation factors (GDFs), Anti-müllerian hormo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SMAD4
SMAD4, also called SMAD family member 4, Mothers against decapentaplegic homolog 4, or DPC4 (Deleted in Pancreatic Cancer-4) is a highly conserved protein present in all metazoans. It belongs to the SMAD family of transcription factor proteins, which act as mediators of TGF-β signal transduction. The TGFβ family of cytokines regulates critical processes during the lifecycle of metazoans, with important roles during embryo development, tissue homeostasis, regeneration, and immune regulation. SMAD 4 belongs to the co-SMAD group (''common mediator'' SMAD), the second class of the SMAD family. SMAD4 is the only known co-SMAD in most metazoans. It also belongs to the Darwin family of proteins that modulate members of the TGFβ protein superfamily, a family of proteins that all play a role in the regulation of cellular responses. Mammalian SMAD4 is a homolog of the ''Drosophila'' protein "Mothers against decapentaplegic" named Medea. SMAD4 interacts with R-Smads, such as SMAD2, SMA ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Loeys–Dietz Syndrome
Loeys–Dietz syndrome (LDS) is an autosomal dominant genetic connective tissue disorder. It has features similar to Marfan syndrome and Ehlers–Danlos syndrome. The disorder is marked by aneurysms in the aorta, often in children, and the aorta may also undergo sudden dissection in the weakened layers of the wall of the aorta. Aneurysms and dissections also can occur in arteries other than the aorta. Because aneurysms in children tend to rupture early, children are at greater risk for dying if the syndrome is not identified. Surgery to repair aortic aneurysms is essential for treatment. There are five types of the syndrome, labelled types I through V, which are distinguished by their genetic cause. Type 1, Type 2, Type 3, Type 4 and Type 5 are caused by mutations in '' TGFBR1'', ''TGFBR2'', '' SMAD3'', ''TGFB2'', and ''TGFB3'' respectively. These five genes encoding transforming growth factors play a role in cell signaling that promotes growth and development of the body's tissu ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
C-jun
Transcription factor Jun is a protein that in humans is encoded by the ''JUN'' gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the JUN gene. c-jun was the first oncogenic transcription factor discovered. The proto-oncogene c-Jun is the cellular homolog of the viral oncoprotein v-jun (). The viral homolog v-jun was discovered in avian sarcoma virus 17 and was named for ''ju-nana'', the Japanese word for 17. The human JUN encodes a protein that is highly similar to the viral protein, which interacts directly with specific target DNA sequences to regulate gene expression. This gene is intronless and is mapped to 1p32-p31, a chromosomal region involved in both translocations and deletions in human malignancies. Function Regulation Both Jun and its dimerization partners in AP-1 formation are subject to regulation by diverse extr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
C-myc
''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' (MYC), ''l-myc'' (MYCL), and ''n-myc'' (MYCN). ''c-myc'' (also sometimes referred to as ''MYC'') was the first gene to be discovered in this family, due to homology with the viral gene ''v-myc''. In cancer, ''c-myc'' is often constitutively (persistently) expressed. This leads to the increased expression of many genes, some of which are involved in cell proliferation, contributing to the formation of cancer. A common human translocation involving ''c-myc'' is critical to the development of most cases of Burkitt lymphoma. Constitutive upregulation of ''Myc'' genes have also been observed in carcinoma of the cervix, colon, breast, lung and stomach. Myc is thus viewed as a promising target for anti-cancer drugs. Unfortunately, Myc possesses several features that render it undruggable such that any anti-cancer drugs f ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Transforming Growth Factor Beta
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other signaling proteins. TGFB proteins are produced by all white blood cell lineages. Activated TGF-β complexes with other factors to form a serine/threonine kinase complex that binds to TGF-β receptors. TGF-β receptors are composed of both type 1 and type 2 receptor subunits. After the binding of TGF-β, the type 2 receptor kinase phosphorylates and activates the type 1 receptor kinase that activates a signaling cascade. This leads to the activation of different downstream substrates and regulatory proteins, inducing transcription of different target genes that function in differentiation, chemotaxis, proliferation, and activation of many immune cells. TGF-β is secreted by many cell types, including macrophages, in a latent form in which it ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chromosome 15 (human)
Chromosome 15 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 15 spans about 102 million base pairs (the building material of DNA) and represents between 3% and 3.5% of the total DNA in cells. Chromosome 15 is an acrocentric chromosome, with a very small short arm (the "p" arm, for "petite"), which contains few protein coding genes among its 19 million base pairs. It has a larger long arm (the "q" arm) that is gene rich, spanning about 83 million base pairs. The human leukocyte antigen gene for β2-microglobulin is found on chromosome 15, as well as the FBN1 gene, coding for both fibrillin-1 (a protein critical to the proper functioning of connective tissue), and aprosin (a small protein produced from part of the transcribed FBN1 gene mRNA), which is involved in fat metabolism. Genes Number of genes The following are some of the gene count estimates of human chromosome 15. Because researchers use different approac ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 basic ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
WWTR1
WW domain-containing transcription regulator protein 1 (WWTR1), also known as Transcriptional coactivator with PDZ-binding motif (TAZ), is a protein that in humans is encoded by the ''WWTR1'' gene. WWTR1 acts as a transcriptional coregulator and has no effect on transcription alone. When in complex with transcription factor binding partners, WWTR1 helps promote gene expression in pathways associated with development, cell growth and survival, and inhibiting apoptosis. Aberrant WWTR1 function has been implicated for its role in driving cancers. WWTR1 is often referred to as TAZ due to its initial characterization with the name TAZ. However, WWTR1 (TAZ) is not to be confused with the protein tafazzin, which originally held the official gene symbol TAZ, and is now TAFAZZIN. Structure WWTR1 contains a proline rich region, TEAD binding motif, WW domain, coiled coil region, and a transactivation domain (TAD) containing the PDZ domain-binding motif. WWTR1 (TAZ) lacks a DNA bin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CXCR4
C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the ''CXCR4'' gene. The protein is a CXC chemokine receptor. Function CXCR-4 is an alpha-chemokine receptor specific for stromal-derived-factor-1 ( SDF-1 also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes. CXCR4 is one of several chemokine co-receptors that HIV can use to infect CD4+ T cells. HIV isolates that use CXCR4 are traditionally known as T-cell tropic isolates. Typically, these viruses are found late in infection. It is unclear as to whether the emergence of CXCR4-using HIV is a consequence or a cause of immunodeficiency. CXCR4 is upregulated during the implantation window in natural and hormone replacement therapy cycles in the endometrium, producing, in presence of a human blastocyst, a surface polarization of the CXCR4 receptors suggesting that this receptor is implicated in t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
TRIM33
E3 ubiquitin-protein ligase TRIM33, also known as (ectodermin homolog and tripartite motif-containing 33) is a protein encoded in the human by the gene ''TRIM33'', a member of the tripartite motif family. TRIM33 is thought to be a transcriptional corepressor. However unlike the related TRIM24 and TRIM28 proteins, few transcription factors such as SMAD4 that interact with TRIM33 have been identified. Structure The protein is a member of the tripartite motif family. This motif includes three zinc-binding domains: * RING * B-box type 1 zinc finger * B-box type 2 zinc finger and a coiled-coil region. Three alternatively spliced transcript variants for this gene have been described, however, the full-length nature of one variant has not been determined. Interactions TRIM33 has been shown to interact with TRIM24. Role in cancer ''TRIM33'' acts as a tumor suppressor gene preventing the development chronic myelomonocytic leukemia. TRIM33 regulates also the TRIM28 receptor and p ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pathogenesis
Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pathos'' 'suffering, disease' and γένεσις ''genesis'' 'creation'. Description Types of pathogenesis include microbial infection, inflammation, malignancy and tissue breakdown. For example, bacterial pathogenesis is the process by which bacteria cause infectious illness. Most diseases are caused by multiple processes. For example, certain cancers arise from dysfunction of the immune system (skin tumors and lymphoma after a renal transplant, which requires immunosuppression), Streptococcus pneumoniae is spread through contact with respiratory secretions, such as saliva, mucus, or cough droplets from an infected person and colonizes the upper respiratory tract and begins to multiply. The pathogenic mechanisms of a disease (or cond ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
