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:". ...
Cyclin T2 antibody LS-C342834 is an unconjugated mouse monoclonal antibody to human Cyclin T2 (CCNT2 ). Validated for DB and WB.
The human cytomegalovirus (HCMV)-encoded protein kinase, pUL97, is considered a cyclin-dependent kinase (CDK) ortholog, due to shared structural and functional characteristics. The primary mechanism of CDK activation is binding to corresponding cyclins, including cyclin T1, which is the usual regulatory cofactor of CDK9. This study provides evidence of direct interaction between pUL97 and cyclin T1 using yeast two-hybrid and co-immunoprecipitation analyses. Confocal immunofluorescence revealed partial colocalization of pUL97 with cyclin T1 in subnuclear compartments, most pronounced in viral replication centres. The distribution patterns of pUL97 and cyclin T1 were independent of HCMV strain and host cell type. The sequence domain of pUL97 responsible for the interaction with cyclin T1 was between amino acids 231-280. Additional co-immunoprecipitation analyses showed cyclin B1 and cyclin A as further pUL97 interaction partners. Investigation of the pUL97-cyclin T1 interaction in an ATP consumption assay
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Amino acids M1 - K726 (end) of human Cyclin T1. Residue M232 of the fusion protein is equivalent to M11 of the native enzyme. The GST tag is located at residues 1 - 220 ...
Author Summary Monocytes do not support HIV-1 replication, in part because they do not express adequate levels of essential cellular cofactors that mediate steps in the viral replication cycle. Monocytes become permissive for viral replication upon differentiation to macrophages, indicating that cellular cofactors are induced during the differentiation process. One such cofactor is Cyclin T1, which is not expressed in monocytes and is expressed at high levels following macrophage differentiation. Cyclin T1 functions to greatly stimulate the amount of HIV-1 produced in the infected cell. We identified a microRNA (miRNA) named miR-198 that represses the expression of Cyclin T1 in monocytes. miRNAs block expression of proteins by binding to messenger RNAs and preventing their translation by ribosomes. The expression levels of miR-198 are greatly reduced in macrophages, and this appears to allow translation of Cyclin T1 mRNA and expression of Cyclin T1 protein. Our study indicates that this miRNA restricts
Cyclin T1 Antibody 20992-1-AP has been identified with WB, ELISA. 20992-1-AP detected 87 kDa band in K-562 cells with 1:200-1:1000 dilution...
Rabbit polyclonal Cyclin T1 antibody validated for WB, IP, ELISA, IHC and tested in Human, Mouse and Rat. Referenced in 10 publications.
Mouse monoclonal Cyclin T2 antibody [2128C1a] validated for WB, Dot and tested in Human. Referenced in 2 publications. Immunogen corresponding to recombinant…
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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
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
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 ...
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 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.
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
Murine fibroblasts expressing viral receptors and human cyclin T1 allow HIV-1 entry and viral gene expression but do not support efficient assembly. A chimeric HIV-1 carrying a non-homologous matrix (MA) from murine leukemia virus in place of HIV-1 MA can assemble efficiently in murine cells, yet has poor infectivity. Here, we assess the ability of a homologous MA from SIV MAC239 to complement assembly and infection in chimeric viruses designated SHIV(MA). The resulting SHIV(MA) chimeras produce more virus than native HIV-1 when transfected into murine cells. SHIV(MA) exhibits cell-type-specific replication in human T cell lines, replicating well in MT4 cells and poorly in Jurkat cells due to an incompatibility with the HIV-1 Env. The infectivity defects of SHIV(MA) are rescued by pseudotyping with VSV-G but not by truncation of the cytoplasmic tail of Env. Passage of SHIV(MA) in Jurkat cells produces variants with improved Env incorporation and improved replication in Jurkat but not in 3T3 TXC ...
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...
A series of mono-pyrrolo[2,3-d]pyrimidines 4a-4k, unsymmetrical bis-purine isosteres 5a-5e and symmetrical bis-pyrrolo[2,3-d]pyrimidines 6a and 6b connected via di(1,2,3-triazolyl)phenyl linker were synthesized by click chemistry. Whereas mono- 4g and bis-pseudopurine 5e showed selective inhibitory activities on cervical carcinoma (HeLa) cells, bis-pyrrolo[2,3-d]pyrimidine 6b exhibited potent and selective anti-proliferative effect in the nanomolar range on pancreatic carcinoma (CFPAC-1) cells. Among these, compound 6b induced a significant reduction in the expression level of CDK9 (cyclin-dependent kinase 9)/cyclin T1 in CFPAC-1 cells concomitant with attenuation of proliferative signaling mediated by c-Raf (rapidly accelerated fibrosarcoma) and p38 MAP (mitogen-activated protein) kinases ...
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 ...
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Plasmid -962 human cyclin D1 promoter EtsB site mutant pGL3Basic from Dr. Frank McCormicks lab contains the insert CCND1 and is published in Nature. 1999 Apr 1;398(6726):422-6. This plasmid is available through Addgene.
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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 …
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 ...
An Intron-Retaining Splice Variant of Human Cyclin A2, Expressed in Adult Differentiated Tissues, Induces a G1-S Cell Cycle Arrest In Vitro. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.