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BRD4
Bromodomain-containing protein 4 is a protein that in humans is encoded by the ''BRD4'' gene. BRD4 is a member of the BET (bromodomain and extra terminal domain) family, which also includes BRD2, BRD3, and BRDT. BRD4, similar to other BET family members, contains two bromodomains that recognize acetylated lysine residues. BRD4 also has an extended C-terminal domain with little sequence homology to other BET family members. Structure The two bromodomains in BRD4, termed BD1 and BD2, consist of 4 alpha-helices linked by 2 loops. The ET domain structure is made up of 3 alpha-helices and a loop. The C-terminal domain of BRD4 has been implicated in promoting gene transcription through interaction with the transcription elongation factor P-TEFb and RNA polymerase II. Function The protein encoded by this gene is homologous to the murine protein MCAP, which associates with chromosomes during mitosis, and to the human BRD2 (RING3) protein, a serine/threonine kinase. Each of the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BET Inhibitors
BET inhibitors are a class of drugs that reversibly bind the bromodomains of Bromodomain and Extra-Terminal motif (BET) proteins BRD2, BRD3, BRD4, and BRDT, and prevent protein-protein interaction between BET proteins and acetylated histones and transcription factors. Discovery and development Thienodiazepine BET inhibitors were discovered by scientists at Yoshitomi Pharmaceuticals (now Mitsubishi Tanabe Pharma) in the early 1990s, and their potential both as anti-inflammatories and anti-cancer agents noted. However, these molecules remained largely unknown until 2010 when both the use of JQ1 in NUT midline carcinoma and of I-BET 762 in sepsis were published. Since this time a number of molecules have been described that are capable of targeting BET bromodomains. BET inhibitors have been described that are able to discriminate between the first and second bromodomains of BET proteins (BD1 vs BD2). However, no BET inhibitor has yet been described that can reliably distinguish ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BRD3
Bromodomain-containing protein 3 (BRD3) also known as RING3-like protein (RING3L) is a protein that in humans is encoded by the BRD3 gene. This gene was identified based on its homology to the gene encoding the RING3 (BRD2) protein, a serine/threonine kinase. The gene maps to 9q34, a region which contains several major histocompatibility complex (MHC) genes. Structure BRD3 is a member of the Bromodomain and Extra-Terminal motif (BET) protein family. Like other BET family members it contains two tandem homologous bromodomains and an "Extra-Terminal" motif. BRD3, similar to BRD2, does not have a long C-terminal domain as BET family proteins BRD4 and BRDT do. Function Like other BET protein family members, BRD3 associates with acetylated lysine residues on histones and transcription factors. BRD3 has been implicated in nucleosome remodeling in the context of transcription. In addition, BRD3 has been shown to interact with RNA molecules and form protein-RNA aggregates. B ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
NUT Midline Carcinoma
NUT carcinoma (NC; formerly NUT midline carcinoma (NMC)) is a rare genetically defined, very aggressive squamous cell epithelial cancer that usually arises in the midline of the body and is characterized by a chromosomal rearrangement in the nuclear protein in testis gene (i.e. ''NUTM1'' gene). In approximately 75% of cases, the coding sequence of ''NUTM1'' in band 14 on the long (or "q") arm of chromosome 15 is fused to '' BRD4'' or '' BRD3'', which creates a chimeric gene that encodes the ''BRD-NUT'' fusion protein. The remaining cases, the fusion of NUTM1 is to an unknown partner gene, usually called ''NUT''-variant. The name NUT carcinoma was introduced as the carcinoma does not only occur in the body midline; therefore, WHO also changed the name in 2015 in the WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. Signs and symptoms In the United States, about 20–30 cases are reported each year. This may be a gross underestimate of the total number of cases ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bromodomain
A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the ''N''-terminal tails of histones. Bromodomains, as the "readers" of lysine acetylation, are responsible in transducing the signal carried by acetylated lysine residues and translating it into various normal or abnormal phenotypes. Their affinity is higher for regions where multiple acetylation sites exist in proximity. This recognition is often a prerequisite for protein-histone association and chromatin remodeling. The domain itself adopts an all-α protein fold, a bundle of four alpha helices each separated by loop regions of variable lengths that form a hydrophobic pocket that recognizes the acetyl lysine. Discovery The bromodomain was identified as a novel structural motif by John W. Tamkun and colleagues studying the drosophila gene ''Brahma''/''brm'', and showed sequence similarity to genes involved in transcriptional activation. The name "bromo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
RFC3
Replication factor C subunit 3 is a protein that in humans is encoded by the ''RFC3'' gene. Function The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell nuclear antigen (PCNA) and replication factor C (RFC). RFC, also named activator 1, is a protein complex consisting of five distinct subunits of 140, 40, 38, 37, and 36 kDa. This gene encodes the 38 kDa subunit. This subunit is essential for the interaction between the 140 kDa subunit and the core complex that consists of the 36, 37, and 40 kDa subunits. Alternatively spliced transcript variants encoding distinct isoforms have been described. Interactions RFC3 has been shown to interact with: * BRD4, * CHTF18, * PCNA, * RFC1, and * RFC4 Replication factor C subunit 4 is a protein that in humans is encoded by the ''RFC4'' gene. Function The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon r ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GATA1
GATA-binding factor 1 or GATA-1 (also termed Erythroid transcription factor) is the founding member of the GATA family of transcription factors. This protein is widely expressed throughout vertebrate species. In humans and mice, it is encoded by the ''GATA1'' and ''Gata1'' genes, respectively. These genes are located on the X chromosome in both species. GATA1 regulates the expression (i.e. formation of the genes' products) of an ensemble of genes that mediate the development of red blood cells and platelets. Its critical roles in red blood cell formation include promoting the maturation of precursor cells, e.g. erythroblasts, to red blood cells and stimulating these cells to erect their cytoskeleton and biosynthesize their oxygen-carrying components viz., hemoglobin and heme. GATA1 plays a similarly critical role in the maturation of blood platelets from megakaryoblasts, promegakaryocytes, and megakaryocytes; the latter cells then shed membrane-enclosed fragments of their cytop ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
RFC2
Replication factor C subunit 2 is a protein that in humans is encoded by the ''RFC2'' gene. Function The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins, proliferating cell nuclear antigen (PCNA) and replication factor C (RFC). RFC, also called activator 1, is a protein complex consisting of five distinct subunits of 145, 40, 38, 37, and 36.5 kD. This gene encodes the 40 kD subunit, which has been shown to be responsible for binding ATP. Deletion of this gene has been associated with Williams syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been described. Interactions RFC2 has been shown to interact with BRD4, CHTF18, PCNA, RFC4 and RFC5 Replication factor C subunit 5 is a protein that in humans is encoded by the ''RFC5'' gene. Function The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins prolife ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
P-TEFb
The positive transcription elongation factor, P-TEFb, is a multiprotein complex that plays an essential role in the regulation of transcription by RNA polymerase II (Pol II) in eukaryotes. Immediately following initiation Pol II becomes trapped in promoter proximal paused positions on the majority of human genes (Figure 1). P-TEFb is a cyclin dependent kinase that can phosphorylate the DRB sensitivity inducing factor (DSIF) and negative elongation factor (NELF), as well as the carboxyl terminal domain of the large subunit of Pol IIMarshall NF, Peng J, Xie Z, Price DH. Control of RNA polymerase II elongation potential by a novel carboxyl-terminal domain kinase. J Biol Chem 1996; 271:27176-83. and this causes the transition into productive elongation leading to the synthesis of mRNAs. P-TEFb is regulated in part by a reversible association with the 7SK snRNP.Peterlin BM, Brogie JE, Price DH. 7SK snRNA: a noncoding RNA that plays a major role in regulating eukaryotic transcription. Wi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
RFC1
Replication factor C subunit 1 is a protein that in humans is encoded by the ''RFC1'' gene. Function The protein encoded by this gene is the large subunit of replication factor C, which is a five subunit DNA polymerase accessory protein. Replication factor C is a DNA-dependent ATPase that is required for eukaryotic DNA replication and repair. The protein acts as an activator of DNA polymerases, binds to the 3' end of primers, and promotes coordinated synthesis of both strands. It also may have a role in telomere stability. Interactions RFC1 has been shown to interact with: * BRD4, * HDAC1, * PCNA, * RELA and * RFC3 Replication factor C subunit 3 is a protein that in humans is encoded by the ''RFC3'' gene. Function The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell n .... Clinical relevance Biallelic intronic repeat expansions (a series of repeating nucleotide sequences) in t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
RFC4
Replication factor C subunit 4 is a protein that in humans is encoded by the ''RFC4'' gene. Function The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell nuclear antigen (PCNA) and replication factor C (RFC). RFC, also named activator 1, is a protein complex consisting of five distinct subunits of 140, 40, 38, 37, and 36 kD. This gene encodes the 37 kD subunit. This subunit forms a core complex with the 36 and 40 kDa subunits. The core complex possesses DNA-dependent ATPase activity, which was found to be stimulated by PCNA in an in vitro system. Alternatively spliced transcript variants encoding the same protein have been reported. Interactions RFC4 has been shown to interact with: * BRD4, * CHTF18, * PCNA, * RFC2, * RFC3, and * RFC5 Replication factor C subunit 5 is a protein that in humans is encoded by the ''RFC5'' gene. Function The elongation of primed DNA templates by ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
RFC5
Replication factor C subunit 5 is a protein that in humans is encoded by the ''RFC5'' gene. Function The elongation of primed DNA templates by DNA polymerase delta and DNA polymerase epsilon requires the accessory proteins proliferating cell nuclear antigen (PCNA) and replication factor C (RFC). RFC, also named activator 1, is a protein complex consisting of five distinct subunits of 140, 40, 38, 37, and 36 kD. This gene encodes the 36 kD subunit. This subunit can interact with the C-terminal region of PCNA. It forms a core complex with the 38 and 40 kDa subunits. The core complex possesses DNA-dependent ATPase activity, which was found to be stimulated by PCNA in an in vitro system. Alternatively spliced transcript variants encoding distinct isoforms have been reported. Interactions RFC5 has been shown to interact with: * BRD4, * CHTF18, * PCNA, * RFC2, and * RFC4 Replication factor C subunit 4 is a protein that in humans is encoded by the ''RFC4'' gene. Function T ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BRDT
Bromodomain testis-specific protein is a protein that in humans is encoded by the ''BRDT'' gene. It is a member of the Bromodomain and Extra-terminal motif (BET) protein family. BRDT is similar to the RING3 protein family. It possesses 2 bromodomain motifs and a PEST sequence (a cluster of proline, glutamic acid, serine, and threonine residues), characteristic of proteins that undergo rapid intracellular degradation. The bromodomain is found in proteins that regulate transcription. Two transcript variants encoding the same protein have been found for this gene. The use of three different mouse models (Brdt knock-out mice, mice expressing a non-functional Brdt and mice expressing a mutated Brdt lacking its first bromodomain) showed that Brdt drives a meiotic and post-meiotic gene expression program. It also controls the genome-wide post-meiotic genome reorganization that occurs after histone hyperacetylation in elongating spermatids. Model organisms Model organisms have been us ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |