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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 ...
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RNA Polymerase II Elongation Control
Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in Genetic code, coding, Translation (biology), decoding, Regulatory RNA, regulation and Gene expression, expression of genes. RNA and deoxyribonucleic acid (DNA) are nucleic acids. Along with lipids, proteins, and carbohydrates, nucleic acids constitute one of the four major macromolecules essential for all known forms of life. Like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA, RNA is found in nature as a single strand folded onto itself, rather than a paired double strand. Cellular organisms use messenger RNA (''mRNA'') to convey genetic information (using the nucleobase, nitrogenous bases of guanine, uracil, adenine, and cytosine, denoted by the letters G, U, A, and C) that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome. Some RNA molecules play an active role within cells by catalyzing biological reactions, control ...
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Cdk9
Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb. Function The protein encoded by this gene is a member of the cyclin-dependent kinase (CDK) family. CDK family members are highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2, and known as important cell cycle regulators. This kinase was found to be a component of the multiprotein complex TAK/P-TEFb, which is an elongation factor for RNA polymerase II-directed transcription and functions by phosphorylating the C-terminal domain of the largest subunit of RNA polymerase II. This protein forms a complex with and is regulated by its regulatory subunit cyclin T or cyclin K. HIV-1 Tat protein was found to interact with this protein and cyclin T, which suggested a possible involvement of this protein in AIDS. CDK9 is also known to associate with other proteins such as TRAF2, and be involved in differentiation of skeletal muscle. Inhibitors Based on molecular docking resul ...
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HEXIM2
Protein HEXIM2 is a protein that in humans is encoded by the ''HEXIM2'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba .... References Further reading

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HEXIM1
Protein HEXIM1 is a protein that in humans is encoded by the ''HEXIM1'' gene. Interactions HEXIM1 has been shown to interact with Cyclin T1 and Cdk9 Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb. Function The protein encoded by this gene is a member of the cyclin-dependent kinase (CDK) family. CDK family members are highly similar to the gene produ ... References Further reading

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Regulation Of P-TEFb By The 7SK SnRNP
Regulation is the management of complex systems according to a set of rules and trends. In systems theory, these types of rules exist in various fields of biology and society, but the term has slightly different meanings according to context. For example: * in biology, gene regulation and metabolic regulation allow living organisms to adapt to their environment and maintain homeostasis; * in government, typically regulation means stipulations of the delegated legislation which is drafted by subject-matter experts to enforce primary legislation; * in business, industry self-regulation occurs through self-regulatory organizations and trade associations which allow industries to set and enforce rules with less government involvement; and, * in psychology, self-regulation theory is the study of how individuals regulate their thoughts and behaviors to reach goals. Social Regulation in the social, political, psychological, and economic domains can take many forms: legal restrictions ...
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Tat (HIV)
In molecular biology, Tat is a protein that is encoded for by the ''tat'' gene in HIV-1. Tat is a regulatory protein that drastically enhances the efficiency of viral transcription. Tat stands for "Trans-Activator of Transcription". The protein consists of between 86 and 101 amino acids depending on the subtype. Tat vastly increases the level of transcription of the HIV dsDNA. Before Tat is present, a small number of RNA transcripts will be made, which allow the Tat protein to be produced. Tat then binds to cellular factors and mediates their phosphorylation, resulting in increased transcription of all HIV genes, providing a positive feedback cycle. This in turn allows HIV to have an explosive response once a threshold amount of Tat is produced, a useful tool for defeating the body's response. Tat also appears to play a more direct role in the HIV disease process. The protein is released by infected cells in culture, and is found in the blood of HIV-1 infected patients. It can b ...
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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 ...
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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 ...
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Cyclin Dependent Kinase
Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They are present in all known eukaryotes, and their regulatory function in the cell cycle has been evolutionarily conserved. In fact, yeast cells can proliferate normally when their CDK gene has been replaced with the homologous human gene. CDKs are relatively small proteins, with molecular weights ranging from 34 to 40 kDa, and contain little more than the kinase domain. By definition, a CDK binds a regulatory protein called a cyclin. Without cyclin, CDK has little kinase activity; only the cyclin-CDK complex is an active kinase but its activity can be typically further modulated by phosphorylation and other binding proteins, like p27. CDKs phosphorylate their substrates on serines and threonines, so they are serine-threonine kinases. The co ...
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RNA Polymerase II
RNA polymerase II (RNAP II and Pol II) is a multiprotein complex that transcribes DNA into precursors of messenger RNA (mRNA) and most small nuclear RNA (snRNA) and microRNA. It is one of the three RNAP enzymes found in the nucleus of eukaryotic cells. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase. A wide range of transcription factors are required for it to bind to upstream gene promoters and begin transcription. Discovery Early studies suggested a minimum of two RNAPs: one which synthesized rRNA in the nucleolus, and one which synthesized other RNA in the nucleoplasm, part of the nucleus but outside the nucleolus. In 1969, science experimentalists Robert Roeder and William Rutter definitively discovered an additional RNAP that was responsible for transcription of some kind of RNA in the nucleoplasm. The finding was obtained by the use of ion-exchange chromatography via DEAE coated Sephadex beads. The technique separated the enzymes ...
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HIV Tat P-TEFb Structure
The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype. In most cases, HIV is a sexually transmitted infection and occurs by contact with or transfer of blood, pre-ejaculate, semen, and vaginal fluids. Non-sexual transmission can occur from an infected mother to her infant during pregnancy, during childbirth by exposure to her blood or vaginal fluid, and through breast milk. Within these bodily fluids, HIV is present as both free virus particles and virus within infected immune cells. Research has shown (for both same-sex and opposite-sex couples) that HIV is untransmittable throug ...
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MRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is created during the process of Transcription (biology), transcription, where an enzyme (RNA polymerase) converts the gene into primary transcript mRNA (also known as pre-mRNA). This pre-mRNA usually still contains introns, regions that will not go on to code for the final amino acid sequence. These are removed in the process of RNA splicing, leaving only exons, regions that will encode the protein. This exon sequence constitutes mature mRNA. Mature mRNA is then read by the ribosome, and, utilising amino acids carried by transfer RNA (tRNA), the ribosome creates the protein. This process is known as Translation (biology), translation. All of these processes form part of the central dogma of molecular biology, which describes the flow of genet ...
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