RNA polymerase II-associated factor 1 (PAF1) (PAF1)

RNA polymerase II-associated factor 1 (PAF1) is a key subunit of the PAF1 complex (PAF1C), which is essential for the regulation of gene expression through its interaction with RNA polymerase II (UniProt P51748). It coordinates various transcriptional processes, including elongation, chromatin remodeling via histone ubiquitination and methylation, and mRNA 3' end processing (PubMed: 30104616). PAF1 is notably overexpressed in several malignancies, most prominently in pancreatic ductal adenocarcinoma, where it is also known as Pancreatic Differentiation 2 (PD2) (PubMed: 23838011). In these contexts, it functions as an oncogene by promoting the expression of genes involved in cell cycle progression and the maintenance of cancer stem cell pluripotency. Therapeutic strategies targeting PAF1 include the development of small molecule inhibitors like iPAF1C that block its interaction with other complex members and RNA-based therapies designed to reduce its mRNA levels (PubMed: 32433314). While targeting PAF1 offers a way to hit oncogenic drivers, its fundamental role in global transcription necessitates careful evaluation of the therapeutic index to avoid widespread cellular dysfunction.

Other names

PD2Pancreatic differentiation 2PAF1 homologRNA polymerase II-associated factor 1 homologPAF1C subunit PAF1

Disruption of the PAF1 complex assembly or recruitment to RNA polymerase II, or targeted degradation of PAF1 mRNA to prevent protein synthesis.