3JVF , 6DF3 , 6GG1
58-504: IL-24 or IL 24 can refer to: Interleukin 24 Illinois's 24th congressional district , an obsolete district Illinois Route 24 Ilyushin -24 Soviet bomber project. The design of the plane based on IL-22 was started after World War II and abandoned along with the IL-22 project. [REDACTED] Topics referred to by the same term This disambiguation page lists articles associated with
116-564: A tumour suppressing protein. IL-24 appears to control cell survival and proliferation by inducing rapid activation of particular transcription factors called STAT1 and STAT3 . This cytokine is predominantly released by activated monocytes , macrophages and T helper 2 (Th2) cells and acts on skin, lung, and reproductive tissues. IL-24 performs important roles in wound healing, arthritis , psoriasis and cancer . Several studies have shown that cell death occurs in cancer cells/cell lines following exposure to IL-24. The gene for IL-24
174-512: A different strength of interaction. For example, although the consensus binding site for the TATA-binding protein (TBP) is TATAAAA, the TBP transcription factor can also bind similar sequences such as TATATAT or TATATAA. Because transcription factors can bind a set of related sequences and these sequences tend to be short, potential transcription factor binding sites can occur by chance if
232-452: A gene on a chromosome into RNA, and then the RNA is translated into protein. Any of these steps can be regulated to affect the production (and thus activity) of a transcription factor. An implication of this is that transcription factors can regulate themselves. For example, in a negative feedback loop, the transcription factor acts as its own repressor: If the transcription factor protein binds
290-421: A host cell to promote pathogenesis. A well studied example of this are the transcription-activator like effectors ( TAL effectors ) secreted by Xanthomonas bacteria. When injected into plants, these proteins can enter the nucleus of the plant cell, bind plant promoter sequences, and activate transcription of plant genes that aid in bacterial infection. TAL effectors contain a central repeat region in which there
348-773: A living cell. Additional recognition specificity, however, may be obtained through the use of more than one DNA-binding domain (for example tandem DBDs in the same transcription factor or through dimerization of two transcription factors) that bind to two or more adjacent sequences of DNA. Transcription factors are of clinical significance for at least two reasons: (1) mutations can be associated with specific diseases, and (2) they can be targets of medications. Due to their important roles in development, intercellular signaling, and cell cycle, some human diseases have been associated with mutations in transcription factors. Many transcription factors are either tumor suppressors or oncogenes , and, thus, mutations or aberrant regulation of them
406-417: A major role in determining sex in humans. Cells can communicate with each other by releasing molecules that produce signaling cascades within another receptive cell. If the signal requires upregulation or downregulation of genes in the recipient cell, often transcription factors will be downstream in the signaling cascade. Estrogen signaling is an example of a fairly short signaling cascade that involves
464-853: A methylated CpG site, 175 transcription factors (34%) that had enhanced binding if their binding sequence had a methylated CpG site, and 25 transcription factors (5%) were either inhibited or had enhanced binding depending on where in the binding sequence the methylated CpG was located. TET enzymes do not specifically bind to methylcytosine except when recruited (see DNA demethylation ). Multiple transcription factors important in cell differentiation and lineage specification, including NANOG , SALL4 A, WT1 , EBF1 , PU.1 , and E2A , have been shown to recruit TET enzymes to specific genomic loci (primarily enhancers) to act on methylcytosine (mC) and convert it to hydroxymethylcytosine hmC (and in most cases marking them for subsequent complete demethylation to cytosine). TET-mediated conversion of mC to hmC appears to disrupt
522-431: A proto-oncogene, within tumor cells and inhibiting epithelial cell differentiation. IL-24 also induces apoptosis By inducing more stress on the endoplasmic reticulum. Transcription factor 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
580-452: A smaller number. Therefore, approximately 10% of genes in the genome code for transcription factors, which makes this family the single largest family of human proteins. Furthermore, genes are often flanked by several binding sites for distinct transcription factors, and efficient expression of each of these genes requires the cooperative action of several different transcription factors (see, for example, hepatocyte nuclear factors ). Hence,
638-505: 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
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#1732793173949696-419: Is chromatin immunoprecipitation (ChIP). This technique relies on chemical fixation of chromatin with formaldehyde , followed by co-precipitation of DNA and the transcription factor of interest using an antibody that specifically targets that protein. The DNA sequences can then be identified by microarray or high-throughput sequencing ( ChIP-seq ) to determine transcription factor binding sites. If no antibody
754-531: Is a protein in the interleukin family, a type of cytokine signaling molecule in the immune system. In humans, this protein is encoded by the IL24 gene . IL-24 is a cytokine belonging to the IL-10 family of cytokines that signals through two heterodimeric receptors: IL-20R1 / IL-20R2 and IL-22R1/IL-20R2. This interleukin is also known as melanoma differentiation-associated 7 ( mda-7 ) due to its discovery as
812-450: Is a simple relationship between the identity of two critical residues in sequential repeats and sequential DNA bases in the TAL effector's target site. This property likely makes it easier for these proteins to evolve in order to better compete with the defense mechanisms of the host cell. It is common in biology for important processes to have multiple layers of regulation and control. This
870-578: Is also important in autoimmune diseases such as psoriasis , rheumatoid arthritis or spondyloarthropathy. IL-24 carries its functions through two types of membrane receptors (IL-22R1/IL-20R2 and IL-20R1/IL-20R2) with simultaneous activation of the JAK/signal transducer and activator of transcription ( STAT ) pathway within their cytoplasmic domains. IL-24 is a type of cytokine that interacts frequently with class 2 cytokine receptors. IL-24 can form IL-20R1/IL-20R2 and IL-22R1/IL-20R2 which are shared with
928-455: Is also true with transcription factors: Not only do transcription factors control the rates of transcription to regulate the amounts of gene products (RNA and protein) available to the cell but transcription factors themselves are regulated (often by other transcription factors). Below is a brief synopsis of some of the ways that the activity of transcription factors can be regulated: Transcription factors (like all proteins) are transcribed from
986-522: Is an important candidate for cancer therapy. IL-24 is able to induce apoptosis via both intracellular and extracellular signaling mechanisms. Secreted IL-24 protein induces a robust expression of endogenous IL-24 and subsequent induction of tumor-specific killing through an ER stress-mediated pathway as well as by ROS production. The ER stress is the initial pathway in IL-24-induced apoptosis. An important question, which remained unresolved,
1044-534: Is associated with cancer. Three groups of transcription factors are known to be important in human cancer: (1) the NF-kappaB and AP-1 families, (2) the STAT family and (3) the steroid receptors . Below are a few of the better-studied examples: Approximately 10% of currently prescribed drugs directly target the nuclear receptor class of transcription factors. Examples include tamoxifen and bicalutamide for
1102-595: Is available for the protein of interest, DamID may be a convenient alternative. As described in more detail below, transcription factors may be classified by their (1) mechanism of action, (2) regulatory function, or (3) sequence homology (and hence structural similarity) in their DNA-binding domains. They are also classified by 3D structure of their DBD and the way it contacts DNA. There are two mechanistic classes of transcription factors: Transcription factors have been classified according to their regulatory function: Transcription factors are often classified based on
1160-442: Is called its DNA-binding domain. Below is a partial list of some of the major families of DNA-binding domains/transcription factors: The DNA sequence that a transcription factor binds to is called a transcription factor-binding site or response element . Transcription factors interact with their binding sites using a combination of electrostatic (of which hydrogen bonds are a special case) and Van der Waals forces . Due to
1218-403: Is followed by guanine in the 5' to 3' DNA sequence, a CpG site .) Methylation of CpG sites in a promoter region of a gene usually represses gene transcription, while methylation of CpGs in the body of a gene increases expression. TET enzymes play a central role in demethylation of methylated cytosines. Demethylation of CpGs in a gene promoter by TET enzyme activity increases transcription of
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#17327931739491276-595: Is highly conserved throughout evolution with sequence homology between species including yeast, dog, cat, monkey and cow. It is located on chromosome 1q32-33 in humans along with several other IL-10 cytokine family gene members. IL-24 encompasses seven exons and six introns . The cDNA of IL-24 is 1,718 base pairs in length and encodes a protein of 206 amino acid with a predicted molecular size of ˜24 kDa. IL-24 also contains an IL-10 signature motif at amino acids 101–121 shared by other IL-10 family member cytokines. IL-24 possibly can form functionally active dimers due to
1334-408: Is located on chromosome 1 in humans. The structure of IL-24 has been found through crystallization by fusing a flexible linker with a ligand to its two receptors, IL-22R1 and IL-20R2. The structure revealed that there is a lack of disulfides , which is present in most cytokines, and is likely the reason why IL-24 is unstable compared to other interleukins. IL-24 is a secreted protein that
1392-409: Is not clear that they are "drugable" but progress has been made on Pax2 and the notch pathway. Gene duplications have played a crucial role in the evolution of species. This applies particularly to transcription factors. Once they occur as duplicates, accumulated mutations encoding for one copy can take place without negatively affecting the regulation of downstream targets. However, changes of
1450-414: Is organized with the help of histones into compact particles called nucleosomes , where sequences of about 147 DNA base pairs make ~1.65 turns around histone protein octamers. DNA within nucleosomes is inaccessible to many transcription factors. Some transcription factors, so-called pioneer factors are still able to bind their DNA binding sites on the nucleosomal DNA. For most other transcription factors,
1508-643: Is that both of the above hypotheses are correct. IL-24 is able to induce toxic autophagy in cancer cells in vitro and animal models in vivo. Past independent studies have also proven that the cytokine can play a role in inflammation for inflammatory bowel disease, psoriasis, cardiovascular disease, rheumatoid arthritis, tuberculosis, and viral infection. Secondary cytokines that evoke antitumor immune responses are stimulated by IL-24. These secondary cytokines include TNF-α , IFN-gamma , and IL-1 , which induce apoptosis. IL-24 also inhibits cancer by blocking VEGF and TGF-alpha activities through inhibition of Src ,
1566-628: Is that they contain at least one DNA-binding domain (DBD), which attaches to a specific sequence of DNA adjacent to the genes that they regulate. TFs are grouped into classes based on their DBDs. Other proteins such as coactivators , chromatin remodelers , histone acetyltransferases , histone deacetylases , kinases , and methylases are also essential to gene regulation, but lack DNA-binding domains, and therefore are not TFs. TFs are of interest in medicine because TF mutations can cause specific diseases, and medications can be potentially targeted toward them. Transcription factors are essential for
1624-487: Is why IL-24 has the abilities to selectively induce apoptosis in a large spectrum of human cancer-derived cell lines without harming normal cells. One possible reason for this differential killing effect involves inherent biochemical differences between normal and cancer cells (ER stress, ROS production and ceramide ), another possibility is that IL-24 is able to target a molecule that only triggers apoptosis in cancer cells. The third option for this differential killing effect
1682-514: The TET1 protein that initiates a pathway of DNA demethylation . EGR1, together with TET1, is employed in programming the distribution of methylation sites on brain DNA during brain development and in learning (see Epigenetics in learning and memory ). Transcription factors are modular in structure and contain the following domains : The portion ( domain ) of the transcription factor that binds DNA
1740-920: The estrogen receptor transcription factor: Estrogen is secreted by tissues such as the ovaries and placenta , crosses the cell membrane of the recipient cell, and is bound by the estrogen receptor in the cell's cytoplasm . The estrogen receptor then goes to the cell's nucleus and binds to its DNA-binding sites , changing the transcriptional regulation of the associated genes. Not only do transcription factors act downstream of signaling cascades related to biological stimuli but they can also be downstream of signaling cascades involved in environmental stimuli. Examples include heat shock factor (HSF), which upregulates genes necessary for survival at higher temperatures, hypoxia inducible factor (HIF), which upregulates genes necessary for cell survival in low-oxygen environments, and sterol regulatory element binding protein (SREBP), which helps maintain proper lipid levels in
1798-566: The genomic level, DNA- sequencing and database research are commonly used. The protein version of the transcription factor is detectable by using specific antibodies . The sample is detected on a western blot . By using electrophoretic mobility shift assay (EMSA), the activation profile of transcription factors can be detected. A multiplex approach for activation profiling is a TF chip system where several different transcription factors can be detected in parallel. The most commonly used method for identifying transcription factor binding sites
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1856-427: The preinitiation complex and RNA polymerase . Thus, for a single transcription factor to initiate transcription, all of these other proteins must also be present, and the transcription factor must be in a state where it can bind to them if necessary. Cofactors are proteins that modulate the effects of transcription factors. Cofactors are interchangeable between specific gene promoters; the protein complex that occupies
1914-456: The sequence similarity and hence the tertiary structure of their DNA-binding domains. The following classification is based of the 3D structure of their DBD and the way it contacts DNA. It was first developed for Human TF and later extended to rodents and also to plants. There are numerous databases cataloging information about transcription factors, but their scope and utility vary dramatically. Some may contain only information about
1972-431: The DNA binding specificities of the single-copy Leafy transcription factor, which occurs in most land plants, have recently been elucidated. In that respect, a single-copy transcription factor can undergo a change of specificity through a promiscuous intermediate without losing function. Similar mechanisms have been proposed in the context of all alternative phylogenetic hypotheses, and the role of transcription factors in
2030-411: The DNA of its own gene, it down-regulates the production of more of itself. This is one mechanism to maintain low levels of a transcription factor in a cell. In eukaryotes , transcription factors (like most proteins) are transcribed in the nucleus but are then translated in the cell's cytoplasm . Many proteins that are active in the nucleus contain nuclear localization signals that direct them to
2088-430: The DNA sequence is long enough. It is unlikely, however, that a transcription factor will bind all compatible sequences in the genome of the cell . Other constraints, such as DNA accessibility in the cell or availability of cofactors may also help dictate where a transcription factor will actually bind. Thus, given the genome sequence, it is still difficult to predict where a transcription factor will actually bind in
2146-467: The adjacent gene is either up- or down-regulated . Transcription factors use a variety of mechanisms for the regulation of gene expression. These mechanisms include: Transcription factors are one of the groups of proteins that read and interpret the genetic "blueprint" in the DNA. They bind to the DNA and help initiate a program of increased or decreased gene transcription. As such, they are vital for many important cellular processes. Below are some of
2204-411: The binding of 5mC-binding proteins including MECP2 and MBD ( Methyl-CpG-binding domain ) proteins, facilitating nucleosome remodeling and the binding of transcription factors, thereby activating transcription of those genes. EGR1 is an important transcription factor in memory formation. It has an essential role in brain neuron epigenetic reprogramming. The transcription factor EGR1 recruits
2262-456: 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 of RNA polymerase (the enzyme that performs the transcription of genetic information from DNA to RNA) to specific genes. A defining feature of TFs
2320-450: The cell. Many transcription factors, especially some that are proto-oncogenes or tumor suppressors , help regulate the cell cycle and as such determine how large a cell will get and when it can divide into two daughter cells. One example is the Myc oncogene, which has important roles in cell growth and apoptosis . Transcription factors can also be used to alter gene expression in
2378-408: The combinatorial use of a subset of the approximately 2000 human transcription factors easily accounts for the unique regulation of each gene in the human genome during development . Transcription factors bind to either enhancer or promoter regions of DNA adjacent to the genes that they regulate based on recognizing specific DNA motifs. Depending on the transcription factor, the transcription of
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2436-653: The evolution of all species. The transcription factors have a role in resistance activity which is important for successful biocontrol activity. The resistant to oxidative stress and alkaline pH sensing were contributed from the transcription factor Yap1 and Rim101 of the Papiliotrema terrestris LS28 as molecular tools revealed an understanding of the genetic mechanisms underlying the biocontrol activity which supports disease management programs based on biological and integrated control. There are different technologies available to analyze transcription factors. On
2494-692: The first rounds of CD8 cell expansion to prevent uncontrolled T cell responses. After the combination of anti-IgM and CD40-L stimulation, B lymphocytes can also induce IL-24 expression. In response to immune cells, non-lymphoid cells such as melanocytes can also produce IL-24. IL-24 is an immunomodulatory cytokine which can also display broad cancer-specific suppressor effects. The tumor suppressor activities of IL-24 include inhibition of angiogenesis , sensitization to chemotherapy , and induction of cancer-specific apoptosis . Given its ubiquitous apoptotic effect on malignant cells, lack of an effect on normal cells, and absence of significant side effects, IL-24
2552-535: The gene that they regulate. Other transcription factors differentially regulate the expression of various genes by binding to enhancer regions of DNA adjacent to regulated genes. These transcription factors are critical to making sure that genes are expressed in the right cell at the right time and in the right amount, depending on the changing requirements of the organism. Many transcription factors in multicellular organisms are involved in development. Responding to stimuli, these transcription factors turn on/off
2610-469: The gene. The DNA binding sites of 519 transcription factors were evaluated. Of these, 169 transcription factors (33%) did not have CpG dinucleotides in their binding sites, and 33 transcription factors (6%) could bind to a CpG-containing motif but did not display a preference for a binding site with either a methylated or unmethylated CpG. There were 117 transcription factors (23%) that were inhibited from binding to their binding sequence if it contained
2668-594: The important functions and biological roles transcription factors are involved in: In eukaryotes , an important class of transcription factors called general transcription factors (GTFs) are necessary for transcription to occur. Many of these GTFs do not actually bind DNA, but rather are part of the large transcription preinitiation complex that interacts with RNA polymerase directly. The most common GTFs are TFIIA , TFIIB , TFIID (see also TATA binding protein ), TFIIE , TFIIF , and TFIIH . The preinitiation complex binds to promoter regions of DNA upstream to
2726-432: The nature of these chemical interactions, most transcription factors bind DNA in a sequence specific manner. However, not all bases in the transcription factor-binding site may actually interact with the transcription factor. In addition, some of these interactions may be weaker than others. Thus, transcription factors do not bind just one sequence but are capable of binding a subset of closely related sequences, each with
2784-530: The nucleosome should be actively unwound by molecular motors such as chromatin remodelers . Alternatively, the nucleosome can be partially unwrapped by thermal fluctuations, allowing temporary access to the transcription factor binding site. In many cases, a transcription factor needs to compete for binding to its DNA binding site with other transcription factors and histones or non-histone chromatin proteins. Pairs of transcription factors and other proteins can play antagonistic roles (activator versus repressor) in
2842-415: The nucleus. But, for many transcription factors, this is a key point in their regulation. Important classes of transcription factors such as some nuclear receptors must first bind a ligand while in the cytoplasm before they can relocate to the nucleus. Transcription factors may be activated (or deactivated) through their signal-sensing domain by a number of mechanisms including: In eukaryotes, DNA
2900-481: The other IL-20SFCs and IL-22. IL-20SFC is an IL-20 subfamily of cytokines which includes IL-19 , IL-20 , and IL-24. They all signal through the common chain that is IL-20R2. Through these two types of membrane receptors (IL-22R1/IL-20R2 and IL-20R1/IL-20R2), simultaneous activation of the JAK/signal transducer and activator of transcription (STAT) pathway within their cytoplasmic domains. Although it belongs to
2958-718: The presence of potential disulfide bonds. Researchers identified a number of splice variants of IL-24 lacking one or more exons. The signal peptide in IL-24 is two times the length as in other related human cytokines (51 amino acids), and the predicted molecular mass of IL-24 monomer is 18.3 kDa. IL-24 functions as a cytokine (at low concentrations). Its normal physiological role is connected with wound healing (In normal skin cells, it suppress keratinocyte proliferation during wound healing ), and protection against diseases caused by bacteria (for example Mycobacterim tuberculosis , Salmonella typhimurium , Pseudomonas aeruginosa ). It
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#17327931739493016-503: The promoter DNA and the amino acid sequence of the cofactor determine its spatial conformation. For example, certain steroid receptors can exchange cofactors with NF-κB , which is a switch between inflammation and cellular differentiation; thereby steroids can affect the inflammatory response and function of certain tissues. Transcription factors and methylated cytosines in DNA both have major roles in regulating gene expression. (Methylation of cytosine in DNA primarily occurs where cytosine
3074-515: The regulation of gene expression and are, as a consequence, found in all living organisms. The number of transcription factors found within an organism increases with genome size, and larger genomes tend to have more transcription factors per gene. There are approximately 2800 proteins in the human genome that contain DNA-binding domains, and 1600 of these are presumed to function as transcription factors, though other studies indicate it to be
3132-425: The regulation of the same gene . Most transcription factors do not work alone. Many large TF families form complex homotypic or heterotypic interactions through dimerization. For gene transcription to occur, a number of transcription factors must bind to DNA regulatory sequences. This collection of transcription factors, in turn, recruit intermediary proteins such as cofactors that allow efficient recruitment of
3190-506: The same group of cytokines as IL-10 , it has different effect on the immune system. IL-10 is a suppressive cytokine that suppresses inflammation while also maintaining immunomodulatory functions. Beside the normal physiological roles, IL-24 inhibits tumor growth, invasion, metastasis and angiogenesis . IL-24 can be produced by myeloid cells (in response to microbial products through TLRs ), lymphoid cells , and epithelial cells in response to cytokine stimulation. IL-24 can also dampen
3248-794: The same title formed as a letter–number combination. If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=IL-24&oldid=750459048 " Category : Letter–number combination disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages Interleukin 24 11009 93672 ENSG00000162892 ENSMUSG00000026420 Q13007 Q925S4 NM_001185156 NM_001185157 NM_001185158 NM_006850 NM_181339 NM_053095 NP_001172085 NP_001172086 NP_001172087 NP_006841 NP_444325 Interleukin 24 (IL-24)
3306-447: The transcription of the appropriate genes, which, in turn, allows for changes in cell morphology or activities needed for cell fate determination and cellular differentiation . The Hox transcription factor family, for example, is important for proper body pattern formation in organisms as diverse as fruit flies to humans. Another example is the transcription factor encoded by the sex-determining region Y (SRY) gene, which plays
3364-495: The treatment of breast and prostate cancer , respectively, and various types of anti-inflammatory and anabolic steroids . In addition, transcription factors are often indirectly modulated by drugs through signaling cascades . It might be possible to directly target other less-explored transcription factors such as NF-κB with drugs. Transcription factors outside the nuclear receptor family are thought to be more difficult to target with small molecule therapeutics since it
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