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Study reports 2.53 A atomic structures of both the human PAF1/CTR9 and yeast Paf1/Ctr9 heterodimers. Results clearly reveal that the heterodimer of PAF1/CTR9 or Paf1/Ctr9 is the core component of evolutionarily conserved multifunctional polymerase-associated factor 1 complex (Paf1C) and is important for human PAF1C or yeast Paf1C assembly, yeast viability, and Paf1C-mediated histone modifications.
a subset of enhancers can primarily modulate gene expression by controlling the release of paused Pol II in a PAF1-dependent manner.
These results reveal ubiquitin-proteasome system regulation of Paf1 and suggest downregulation of ubiquitin-proteasome system in elevating Paf1's abundance in poorly differentiated cancers.
The various functions of Paf1C, such as the regulation of promoter-proximal pausing and development in higher eukaryotes, are complex and context dependent.
High PAF1 expression is associated with ovarian cancer.
Overexpression of PD2 leads to increased tumorigenicity and metastasis in pancreatic ductal adenocarcinoma.
Propose that degradation of MYC limits the accumulation of MYC/PAF1C complexes during transcriptional activation.
Mechanistic studies indicated that PAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription.
CNOT4 controls the degradation of chromatin-unbound PAF1 via the 26S proteasome.
this study found that Pol II-associated factor 1 (PAF1) is a critical regulator of paused Pol II release, that positive transcription elongation factor b (P-TEFb) directly regulates the initial recruitment of PAF1 complex (PAF1C) to genes, and that the subsequent recruitment of CDK12 is dependent on PAF1C.
This study reveals an evolutionarily conserved role for PAF1 as a regulator of promoter-proximal pausing by RNA Pol II in all metazoans, including human.
PD2 is a novel cancer stem cell (CSC) maintenance protein, loss of which renders the CSCs more susceptible to drug-induced cell death.
Together, these results indicate that human adenovirus E1A uses hBre1 to recruit the hPaf1 complex in order to optimally activate viral early transcription by enhancing transcriptional elongation.
The results show that the Paf1/Leo1 heterodimer is necessary for its binding to histone H3, the histone octamer, and nucleosome in vitro.
E1A changes the function of hBre1 from a ubiquitin ligase involved in substrate selection to a scaffold which recruits hPaf1 as a means to stimulate transcription and transcription-coupled histone modifications.
Data indicate that the Plus3 domain of the Rtf1 subunit mediates Paf1C recruitment to genes by binding a repeating domain within the phosphorylated elongation factor Spt5.
Data show that activation-induced deaminase (AID) associates with RNA polymerase-associated factor 1 (PAF1) through its N-terminal domain.
PAF1c acts as an arginine methyl histone effector that is recruited to promoters and activates a subset of genes, including targets of estrogen signaling.
that hPaf1/PD2 in association with MLL1 regulates methylation of H3K4 residues, as well as interacts and regulates nuclear shuttling of chromatin remodeling protein CHD1, facilitating its function in pancreatic cancer cells
Interaction between the Polymerase Associated Factor complex and Mixed Lineage Leukemia is critical for gene rearranged leukemogenesis.
link Paf1C with PolII elongation and RNA processing indicates that Paf1C subunits could play roles in controlling transcript length through suppression of PolII accumulation at transcription start site (TSS)-proximal pA sites
The PAF1 complex is required for mammalian development, likely through regulation of H3K36me3, indicating a functional conservation of the PAF1 complex from yeast to mammals in vivo.
As part of a cell-intrinsic transcriptional pathway, Paf1 regulates neuronal migration in the brain.
MLL interacts directly with the polymerase associated factor complex (PAFc) via Paf1 and CTR9. PAFc augments MLL and MLL-AF9 mediated transcriptional activation of Hoxa9 and their interaction is essential for leukemogenesis.
show that Paf1/PD2 is overexpressed in mouse embryonic stem cells (ESCs) and is involved in the maintenance of mouse ESCs.
The PAF1 complex differentially regulates cardiomyocyte specification.
This gene encodes a subunit of the polymerase associated factor (PAF1) complex. The PAF1 complex interacts with RNA polymerase II and plays a role in transcription elongation as well as histone modifications including ubiquitylation and methylation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.
RNA polymerase II-associated factor 1 homolog
, pancreatic differentiation protein 2
, PD2-like protein
, paf1, RNA polymerase II associated factor, homolog, like
, Paf1, RNA polymerase II associated factor, homolog