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Eukaryotic gene expression is commonly controlled at the level of RNA polymerase II (RNAPII) pausing subsequent to transcription initiation. Transcription elongation is stimulated by the positive transcription elongation factor b (P-TEFb) kinase, which is suppressed within the 7SK small nuclear ribonucleoprotein (7SK snRNP). However, the biogenesis and functional significance of 7SK snRNP remain poorly understood. Here, we report that LARP7, BCDIN3, and the noncoding 7SK small nuclear RNA (7SK) are vital for the formation and stability of a cell stress-resistant core 7SK snRNP. Our functional studies demonstrate that 7SK snRNP is not only critical for controlling transcription elongation, but also for regulating alternative splicing of pre-mRNAs. Using a transient expression splicing assay, we find that 7SK snRNP disintegration promotes inclusion of an alternative exon via the increased occupancy of P-TEFb, Ser2-phosphorylated (Ser2-P) RNAPII, and the splicing factor SF2/ASF at the minigene. ...
The Positive Transcription Elongation Factor b (P-TEFb) is a complex of Cyclin Dependent Kinase 9 (CDK9) with either cyclins T1, T2 or K. The complex phosphorylates the C-Terminal Domain of RNA polymerase II (RNAPII) and negative elongation factors, stimulating productive elongation by RNAPII, which is paused after initiation. P-TEFb is recruited downstream of the promoters of many genes, including primary response genes, upon certain stimuli. Flavopiridol (FVP) is a potent pharmacological inhibitor of CDK9 and has been used extensively in cells as a means to inhibit CDK9 activity. Inhibition of P-TEFb complexes has potential therapeutic applications. It has been shown that Lipopolysaccharide (LPS) stimulates the recruitment of P-TEFb to Primary Response Genes (PRGs) and proposed that P-TEFb activity is required for their expression, as the CDK9 inhibitor DRB prevents localization of RNAPII in the body of these genes. We have previously determined the effects of FVP in global gene expression in a
The negative elongation factor NELF is a key component of an early elongation checkpoint generally located within 100 bp of the transcription start site of protein-coding genes. Negotiation of this checkpoint and conversion to productive elongation require phosphorylation of the carboxy-terminal domain of RNA polymerase II (pol II), NELF, and DRB sensitivity-inducing factor (DSIF) by positive transcription elongation factor b (P-TEFb). P-TEFb is dispensable for transcription of the noncoding U2 snRNA genes, suggesting that a NELF-dependent checkpoint is absent. However, we find that NELF at the end of the 800-bp U2 gene transcription unit and RNA interference-mediated knockdown of NELF causes a termination defect. NELF is also associated 800 bp downstream of the transcription start site of the beta-actin gene, where a late P-TEFb-dependent checkpoint occurs. Interestingly, both genes have an extended nucleosome-depleted region up to the NELF-dependent control point. In both cases, transcription
Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. This complex is inactive when in the 7SK snRNP complex form. Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR and the negative elongation factors DSIF and NELF. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis. P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export. Modulates a complex network of chromatin modifications including
The native capacity of adult skeletal muscles to regenerate is vital to the recovery from physical injuries and dystrophic diseases. Currently, the development of therapeutic interventions has been hindered by the complex regulatory network underlying the process of muscle regeneration. Using a mouse model of skeletal muscle regeneration after injury, we identified hexamethylene bisacetamide inducible 1 (HEXIM1, also referred to as CLP-1), the inhibitory component of the positive transcription elongation factor b (P-TEFb) complex, as a pivotal regulator of skeletal muscle regeneration. Hexim1-haplodeficient muscles exhibited greater mass and preserved function compared with those of WT muscles after injury, as a result of enhanced expansion of satellite cells. Transplanted Hexim1-haplodeficient satellite cells expanded and improved muscle regeneration more effectively than WT satellite cells. Conversely, HEXIM1 overexpression restrained satellite cell proliferation and impeded muscle ...
Essential member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to production elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) and spt-5.
Transcription factor IIS cooperates with the E3 ligase UBR5 to ubiquitinate the CDK9 subunit of the positive transcription elongation factor B ...
Recombinant Human Negative elongation factor B Protein. Synthesized in e. coli. Protein Tag: GST. Purity: Greater than 90% as determined by SDS-PAGE. From $88
HIV-1 Tat protein recruits human positive transcription elongation factor P-TEFb, consisting of CDK9 and cyclin T1, to HIV-1 transactivation response (TAR) RNA. CDK9 is maintained in dephosphorylated state by TFIIH and undergo phosphorylation upon the dissociation of TFIIH. Thus, dephosphorylation of CDK9 prior to its association with HIV-1 preinitiation complex might be important for HIV-1 transcription. Others and we previously showed that protein phosphatase-2A and protein phosphatase-1 regulates HIV-1 transcription. In the present study we analyze relative contribution of PP2A and PP1 to dephosphorylation of CDK9 and to HIV-1 transcription in vitro and in vivo. In vitro, PP2A but not PP1 dephosphorylated autophosphorylated CDK9 and reduced complex formation between P-TEFb, Tat and TAR RNA. Inhibition of PP2A by okadaic acid inhibited basal as well as Tat-induced HIV-1 transcription whereas inhibition of PP1 by recombinant nuclear inhibitor of PP1 (NIPP1) inhibited only Tat-induced transcription in
EC 3.1, ELOABP1elongin A-binding protein 1, EloA-BP1REX1, Elongin-A-binding protein 1, KIAA1138elongin A binding protein 1, REX1, RNA exonuclease 1 homolog (S. cerevisiae), TCEB3BP1RNA exonuclease 1 homolog, transcription elongation factor B polypeptide 3 binding protein 1, Transcription elongation factor B polypeptide 3-binding protein ...
The release of paused RNA polymerase II into productive elongation is highly regulated, especially at genes that affect human development and disease. To exert control over this rate-limiting step, we designed sequence-specific synthetic transcription elongation factors (Syn-TEFs). These molecules a …
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
While acetylation levels are regulated by HATs (writers) and HDACs (erasers), acetylation marks are recognised by bromodomains, which can be found in chromatin-associated and transcription-associated proteins that drive the formation of protein complexes that mediate active transcription.13 The bromodomain and extraterminal (BET) domain family of proteins (BRD2, BRD3, BRD4 and BRDT) constitutes the probably best characterised group of chromatin reader proteins in cancer.51 By binding to acetylated chromatin via their tandem-bromodomains, BET proteins regulate the transcription of specific subsets of genes, including those that promote cell-cycle progression and the evasion of apoptosis.52 Furthermore, BET proteins function as critical mediators of transcriptional elongation by promoting the recruitment and activation of the positive transcription elongation factor-b complex (P-TEFb).53 Based on the importance of BET proteins in controlling important numerous cancer-relevant genes such as ...
In a gene trap screen we recovered a mouse mutant line in which an insertion generated a null allele of the Brd4 gene. Brd4 belongs to the Fsh/Brd family, a group of structurally related proteins characterized by the association of two bromodomains and one extraterminal domain. Members of this family include Brd2/Ring3/Fsrg1 in mammals, fs(1)h in Drosophila, and Bdf1 in Saccharomyces cerevisiae. Brd4 heterozygotes display pre- and postnatal growth defects associated with a reduced proliferation rate. These mice also exhibit a variety of anatomical abnormalities: head malformations, absence of subcutaneous fat, cataracts, and abnormal liver cells. In primary cell cultures, heterozygous cells also display reduced proliferation rates and moderate sensitivity to methyl methanesulfonate. Embryos nullizygous for Brd4 die shortly after implantation and are compromised in their ability to maintain an inner cell mass in vitro, suggesting a role in fundamental cellular processes. Finally, sequence ...
Active Motif provides a large number of recombinant bromodomain proteins for studies of bromodomain function in transcriptional regulation and chromatin remodeling.
These findings demonstrate that JMJD3 is simply not very important for RNAPII preliminary focusing on to promoters. Then we tested if JMJD3 has an effect on the amounts of elongating RNAPII at transcribing areas on TGF remedy. ChIP assays showed a clear enrichment in RNAPII-S2p on you can check here the Neurog2 gene immediately after TGF treatment method in C KD cells, correlating with mRNA accumulation. Of interest, this RNAPII-S2p recruitment was absent in JMJD3 KD cells, in agreement with all the lack of lively transcription. To further have an understanding of the influence of JMJD3 on RNAPII-S2p, we analyzed the recruitment within the P-TEFb elongation issue. The catalytic subunit of P-TEFb complex is Cdk9, which phosphorylates Ser-2 of your CTD domain of RNAPII. Aside from its in depth purpose as an critical factor for transcription elongation, it had been also uncovered that Cdk9 phosphorylates Smad3, promoting its activity. On that basis, we examined if JMJD3 regulates Cdk9 binding on ...
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PB1-6 (His)- DESCRIPTION: Human recombinant PB1-6 bromodomain protein expressed with an N-terminal 6xHis-tag in E.coli. ACCESSION #: NM_018313 INCLUDES AMINO ACIDS: 773-917 TAG(S): N-terminal 6xHis-tag MW: 20.0 kDa EXPRESSION SYSTEM: E. coli SUPPLIED
The regulatory cyclin, Cyclin T1 (CycT1), is a host factor essential for HIV-1 replication in CD4 T cells and macrophages. The importance of CycT1 and the Positive Transcription Elongation Factor b (P-TEFb) complex for HIV replication is well-established, but regulation of CycT1 expression and protein levels during HIV replication and latency establishment in CD4 T cells is less characterized. To better define the regulation of CycT1 levels during HIV replication in CD4 T cells, multiparameter flow cytometry was utilized to study the interaction between HIV replication (intracellular p24) and CycT1 of human peripheral blood memory CD4 T cells infected with HIV in vitro. CycT1 was further examined in CD4 T cells of human lymph nodes. In activated (CD3+CD28 costimulation) uninfected blood memory CD4 T cells, CycT1 was most significantly upregulated in maximally activated (CD69+CD25+ and HLA.DR+CD38+) cells. In memory CD4 T cells infected with HIV in vitro, two distinct infected populations of p24+CycT1+
Cyclin-T2 is a protein that in humans is encoded by the CCNT2 gene. The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin and its kinase partner CDK9 were found to be subunits of the transcription elongation factor p-TEFb. The p-TEFb complex containing this cyclin was reported to interact with, and act as a negative regulator of human immunodeficiency virus type 1 (HIV-1) Tat protein. Two alternatively spliced transcript variants, which encode distinct isoforms, have been described. Cyclin T2 has been shown to interact with CDK9 and Retinoblastoma protein. GRCh38: Ensembl release 89: ENSG00000082258 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. ...
This gene encodes a member of the transcription elongation factor A (SII)-like (TCEAL) gene family. This family is comprised of nuclear phosphoproteins that modulate transcription in a promoter context-dependent manner. Multiple family members are located on the X chromosome. Alternatively splicing results in multiple transcript variants. There is a pseudogene for this gene on chromosome 13. [provided by RefSeq, Apr 2015 ...
|p|Structure specific recognition protein 1 (SSRP1) is a subunit of a heterodimer that, along with SUPT16H, forms chromatin transcriptional elongation factor FACT. FACT interacts specifically with histones H2A/H2B to affect nucleosome disassembly and transcription elongation. SSRP1 protein has been
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Once transcription is initiated at the transcription start site (TSS), Pol II pauses at the site just downstream of TSS and requires elongation factors to allow it to proceed. Switching of the RNA Pol II complex from the initiation to the elongation complexes is important for functional transcription, which is mediated by P-TEFb kinase phosphorylating Ser2 position in CTD (Fig. 3A) (Jonkers and Lis, 2015). As assumed, most of the mRNA processing complexes are assembled during the elongation step of transcription (Perales and Bentley, 2009) So chromatin-associated and pol II-interacting mRNA processing proteins are likely to function in regulating transcription elongation (Allemand et al., 2008).. A direct role for SR proteins in transcriptional regulation has been shown for SRSF2. In contrast to shuttling SR proteins (such as SRSF1, SRSF3, and SRSF7), SRSF2 is a non-shuttling protein located in the nucleus. Interestingly, SRSF2 associates with DNA only, but not with cytoplasmic mRNA, suggesting ...
Recent studies have shown that BRD4 has played key roles in the maintenance of aberrant chromatin states in AML, acute lymphoblastic leukemia (ALL), myeloma and lymphoma, and treatment with BRD4 inhibitors could recapitulate anti-leukemic effects in several AML cell lines [35-37]. Initially, the antiproliferative activity of WS-722 was evaluated against THP-1 cells. As shown in Fig. 3A, after treatment for 7 days, WS-722 moderately inhibited growth of THP-1 cells with an IC50 value of 3.86 μmol/L. To confirm whether WS-722 could abrogate BRD4 activity in acute leukemia cell lines, we used the cellular thermal shift assay to study thermal stability of BRD4 upon WS-722 treatment in THP-1 cell line. THP-1 cells were treated with WS-722 and then heated for 3 min at 50 ℃. After freezing in liquid nitrogen and thawing on ice, equal amounts of supernatant were removed and blotted with the BRD4 antibody. Our results suggested that WS-722 stabilized BRD4 in a concentration-dependent manner, suggesting ...
Complete information for TCEANC gene (Protein Coding), Transcription Elongation Factor A N-Terminal And Central Domain Containing, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Iws1 has been implicated in transcriptional elongation by interaction with RNA polymerase II (RNAP II) and elongation factor Spt6 in budding yeast Saccharomyces cerevisiae, and association with transcription factor TFIIS in mammalian cells, but its role in controlling cell growth and proliferation remains unknown. Here we report that the human homolog of Iws1, hIws1, physically interacts with protein arginine methyltransferases PRMT5 which methylates elongation factor Spt5 and regulates its interaction with RNA polymerase II. Gene-specific silencing of hIws1 by RNA interference reveals that hIws1 is essential for cell viability. GFP fusion protein expression approaches demonstrate that the hIws1 protein is located in the nucleus, subsequently, two regions harbored within the hIws1 protein are demonstrated to contain nuclear localization signals (NLSs). In addition, mouse homolog of hiws1 is found to express ubiquitously in various tissues.
The protein encoded by this gene is a subunit of a heterodimer that, along with SUPT16H, forms chromatin transcriptional elongation factor FACT. FACT interacts specifically with histones H2A/H2B to effect nucleosome disassembly and transcription elongation. FACT and cisplatin-damaged DNA may be crucial to the anticancer mechanism of cisplatin. This encoded protein contains a high mobility group box which most likely constitutes the structure recognition element for cisplatin-modified DNA. This protein also functions as a co-activator of the transcriptional activator p63. An alternatively spliced transcript variant of this gene has been described, but its full-length nature is not known ...
The general transcription factor P-TEFb, consisting of Cdk9 and cyclin T, strongly stimulates RNA polymerase II elongation. It is also a host cell cofactor for...
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This application note describes a novel, cell-based assay platform that uses Enzyme Fragment Complementation (EFC) Technology to detect the specific binding and direct protein engagement of potential small molecule inhibitors to G9a methyltransferase and multiple bromodomain proteins. The combination of assay chemistry and liquid handling and detection microplate instrumentation create a simple, robust and definitive cell-based solution for inhibitory compound identification of these important e
Complete information for NELFA gene (Protein Coding), Negative Elongation Factor Complex Member A, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Supplementary MaterialsAdditional file 1: Figure S1 Screening ELISA for 85 B binding scFv in HAL7/8. 1.4 million deaths were reported [1]. Worldwide TB ranks as YM155 reversible enzyme inhibition the second major cause of death from an infectious disease. One third of the world population is estimated to be infected with (Mtb), yet they remain […]. ...
View mouse Hexim1 Chr11:103116231-103119725 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
Petkau, N.; Budak, H.; Zhou, X.; Oster, H.; Eichele, G.: Acetylation of BMAL1 by TIP60 controls BRD4-P-TEFb recruitment to circadian promoters. eLife 8, e43235 (2019 ...
The conviction rate in drug facilitated sexual assault (DFSA) cases is known to be very low. In addition, the potential impact of toxicological results on the case is often not well understood by the judicial authorities. The aims of this study were (1) to obtain more knowledge concerning the prevalence of incapacitating substances in DFSA cases, (2) to create a more efficient DFSA analysis strategy taking background information into account, and (3) to evaluate the potential impact of systematic toxicological analysis (STA) on the final judicial outcome. This small-scale epidemiological study (n = 79) demonstrates that commonly-used illicit drugs, psychoactive medicines and ethanol are more prevalent in DFSA cases in contrast to the highly mediatized date rape drugs. Additionally, via case examples, the interest of performing STA-to prove incapacitation of the victim-in judicial procedures with mutual-consent discussions has been demonstrated as it led to increased convictions. However, more
Bromodomain-containing protein 2 (Brd2) is a BET family chromatin adaptor required for expression of cell cycle associated genes and therefore involved in cell cycle progression. Brd2 is expressed in proliferating neuronal progenitors, displays cell cycle-stimulating activity and, when overexpressed, impairs neuronal differentiation. Paradoxically, Brd2 is also detected in differentiating neurons. To shed light on the role of Brd2 in the transition from cell proliferation to differentiation we have looked for Brd2 interacting proteins upon induction of neuronal differentiation. Surprisingly, we have identified the growth factor Pleiotrophin (Ptn). Ptn antagonizes the cell cycle-stimulating activity associated with Brd2, thus enhancing induced neuronal differentiation. Moreover, Ptn knockdown reduces neuronal differentiation. Ptn-mediated antagonism of Brd2 has been assessed in a cell differentiation model and in two embryonic processes associated with the neural tube: spinal cord neurogenesis ...
Upon recruitment to the viral promoter, P-TEFb and ELL2 act on the same polymerase enzyme to synergistically activate HIV transcription. The sequestration into a SEC and interaction with Tat also stabilize ELL2, which otherwise would be a short-lived protein targeted by the E3 ubiquitin ligase Siah1 for proteasomal degradation. Besides being recruited by Tat/TAR to activate HIV, SEC is also employed by the mixed-lineage leukemia (MLL) protein and its fusion partners to promote the expression of MLL-target genes and leukemogenesis. In addition to SEC, our data indicate that P-TEFb also exists in at least two other complexes (Fig. 1). First, most cellular P-TEFb is normally sequestered in an inactive state in the 7SK snRNP. We have previously identified 7SK snRNA as well as HEXIM1/2, LARP7 and MePCE proteins as key subunits of this complex and determined their roles in inhibiting CDK9 kinase, maintaining 7SK snRNP integrity and suppressing cellular transformation. A number of conditions/reagents ...
The role of bromodomains in translating a deregulated cell acetylome into disease phenotypes was recently unveiled by the development of small molecule bromodomain inhibitors. This breakthrough discovery highlighted bromodomain-containing proteins as key players in cancer biology, as well as inflammation and remyelination in multiple sclerosis.[2] Members of the BET family have been implicated as targets in both human cancer[10][11] and multiple sclerosis.[12] BET inhibitors have shown therapeutic effects in multiple preclinical models of cancer and are currently in clinical trials in the United States.[13] Their application in multiple sclerosis is still in the preclinical stage. Small molecule inhibitors of non-BET bromodomain proteins BRD7 and BRD9 have also been developed.[14][15] ...
Post-translational histone modifications have a critical role in regulating transcription, the cell cycle, DNA replication andDNA damage repair1 . The identification of new histone modifications critical for transcriptional regulation at initiation, elongation or termination is of particular interest. Here we report a new layer of regulation in transcriptional elongation that is conserved from yeast to mammals. This regulation is based on the phosphorylation of a highly conserved tyrosine residue, Tyr 57, in histone H2A and is mediated by the unsuspected tyrosine kinase activity of casein kinase 2 (CK2). Mutation of Tyr 57 in H2Ain yeast or inhibition of CK2 activityimpairs transcriptional elongation in yeast as well asin mammalian cells. Genome-wide binding analysis reveals that CK2a, the catalytic subunit of CK2, binds across RNA-polymerase-II-transcribed coding genes and active enhancers.Mutation of Tyr 57 causes a loss of H2Bmono-ubiquitination as well as H3K4me3 and H3K79me3, histone marks ...
Diese Arbeit setzt ihren Fokus auf die Charakterisierung eines möglichen SPT4-SPT5 Komplex in Arabidopsis thaliana. Die beiden Untereinheiten SPT4 und SPT5 werden von jeweils zwei Genen kodiert: SPT4-1/2 und SPT5-1/2. Eine Mutante bei der die Expression des gewebespezifisch exprimieren SPT5-1 beeinflusst ist, ist lebensfähig, wohingegen die Inaktivierung des allgemein exprimierten SPT5-2 embryonal letal ist. Ein induzierbarer Knockdown der SPT5 Expression führt zu schwerwiegenden Wachstumsdefekten und einer Gewichtsreduktion auf ungefähr 40% des Wildtyps. Ein herunterregulieren der Expression von SPT4-1 und SPT4-2, mittels RNAi, führt zu schweren Wachstums- und Entwicklungsdefekten, bedingt durch eine verminderte Zellproliferation. Zusätzlich zeigen diese Pflanzen auf Auxin zurück zu führende Phänotypen, z.B. eine gestörte Gravitropismusantwort, ein reduziertes Wurzelwachstum und ein verändertes Blattvenenmuster. Übereinstimmend mit diesen Phänotypen zeigte eine genomweite ...
The bromodomain and extraterminal (BET) protein BRD2-4 inhibitors hold therapeutic promise in preclinical models of hematologic malignancies. However, translation of these data to molecules suitable for clinical development has yet to be accomplished. Herein we expand the mechanistic understanding of BET inhibitors in multiple myeloma by using the chemical probe molecule I-BET151. I-BET151 induces apoptosis and exerts strong antiproliferative effect in vitro and in vivo. This is associated with contrasting effects on oncogenic MYC and HEXIM1, an inhibitor of the transcriptional activator P-TEFb. I-BET151 causes transcriptional repression of MYC and MYC-dependent programs by abrogating recruitment to the chromatin of the P-TEFb component CDK9 in a BRD2-4-dependent manner. In contrast, transcriptional upregulation of HEXIM1 is BRD2-4 independent. Finally, preclinical studies show that I-BET762 has a favorable pharmacologic profile as an oral agent and that it inhibits myeloma cell proliferation, resulting
The GreA and GreB transcription elongation factors enable to continuation of RNA transcription past template-encoded arresting sites. Among the Proteobacteria, distinct clades of GreA and GreB are found. GreA differs functionally in that it releases smaller oligonucleotides. Because members of the family outside the Proteobacteria resemble GreA more closely than GreB, the GreB clade (TIGR01461) forms a plausible outgroup and the remainder of the GreA/B family, included in this model, is designated GreA. In the Chlamydias and some spirochetes, the region described by this HMM is found as the C-terminal region of a much larger protein ...
Vincera Pharma, Inc Announces Exclusive License Agreement for Oncology Portfolio Including a Clinical-stage PTEFb/CDK9 Inhibitor and a Preclinical Bioconjugation Platform - read this article along with other careers information, tips and advice on BioSpace
Purpose Transplantation of pancreatic islets to Type 1 diabetes patients is hampered by inflammatory reactions at the transplantation site leading to dysfunction and death of insulin producing beta-cells. decreased phospho-FAK staining in beta-TC6 cell focal adhesions, and (iv) decreased beta-TC6 cell phosphorylation of ERK(T202/Y204), Pyrindamycin A FAK(Y397) and FAK(Y576). Furthermore, co-culture also resulted in cadherin […]. ...
The t(8;21) chromosomal translocation is the most frequently observed translocation in acute myeloid leukemia (AML), the result of which is the expression of th...
Title:Role of Host Factors on the Regulation of Tat-Mediated HIV-1 Transcription. VOLUME: 23 ISSUE: 28. Author(s):Guillaume Mousseau* and Susana T. Valente. Affiliation:The Scripps Research Institute, Department of Immunology and Microbiology, 130 Scripps Way, Jupiter, FL 33458, The Scripps Research Institute, Department of Immunology and Microbiology, 130 Scripps Way, Jupiter, FL 33458. Keywords:Tat, Tat-dependent HIV transcription, HIV latency, P-TEFb, SEC, 7SK snRNP, host factors.. Abstract:Background: The viral transactivator Tat protein is a key modulator of HIV-1 replication, as it regulates transcriptional elongation from the integrated proviral genome. Tat recruits the human transcription elongation factor b, and other host proteins, such as the super elongation complex, to activate the cellular RNA polymerase II, normally stalled shortly after transcription initiation at the HIV promoter. By means of a complex set of interactions with host cellular factors, Tat determines the fate of ...
Specific assembly of ribonucleoprotein complexes is essential in controlling various cellular functions including gene regulation. Diverse scaffolds containing proteins or nucleic acids could play key roles in stabilizing specific ribonucleoprotein complexes by enhancing protein-protein or RNA-protein interactions. One such example is the assembly of active RNA polymerase II transcription elongation complex originating from HIV-1 long terminal repeat promoter that involves HIV-1-encoded Tat protein and viral mRNA structure, trans-activation responsive RNA, and human CyclinT1 which is a subunit of the positive transcription elongation factor complex b. By using genetically encoded fluorescent proteins fused with Tat and human CyclinT1, here we demonstrate that human CyclinT1 was diffused throughout the nucleus and specific interactions between Tat and human CyclinT1 altered the localization of human CyclinT1 to specific nuclear foci. We also found that trans-activation responsive RNA enhanced protein
Link to Pubmed [PMID] - 27058786. Mol. Cell 2016 Apr;62(1):34-46. Studying cancer metabolism gives insight into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a melanoma tumor suppressor that responds to nucleotide stress. HEXIM1 expression is low in melanoma. Its overexpression in a zebrafish melanoma model suppresses cancer formation, while its inactivation accelerates tumor onset in vivo. Knockdown of HEXIM1 rescues zebrafish neural crest defects and human melanoma proliferation defects that arise from nucleotide depletion. Under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to inhibit elongation at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic RNAs to bind to and be stabilized by HEXIM1. HEXIM1 plays an important role in inhibiting cancer cell-specific gene transcription while also ...
Fingerprint Dive into the research topics of Targeting BET Proteins BRD2 and BRD3 in Combination with PI3K-AKT Inhibition as a Therapeutic Strategy for Ovarian Clear Cell Carcinoma. Together they form a unique fingerprint. ...
Aliases : GRMZM2G022987. Description : 27.3.67 RNA.regulation of transcription.putative transcription regulator SPOC domain / Transcription elongation factor S-II protein. ...
1NZ9: Structural and sequence comparisons arising from the solution structure of the transcription elongation factor NusG from Thermus thermophilus
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Alfonso-Dunn R, Turner A-MW, Beltran PMJean, Arbuckle JH, Budayeva HG, Cristea IM, et al. Transcriptional Elongation of HSV Immediate Early Genes by the Super Elongation Complex Drives Lytic Infection and Reactivation from Latency. Cell Host Microbe. 2017 ;21(4):507-517.e5. ...