RNA polymerase II-associated factor 1 (PAF1)

RNA polymerase II-associated factor 1 (PAF1) is a central component of the PAF1 complex (PAF1C), which plays a fundamental role in regulating the transcription cycle of RNA polymerase II, specifically during elongation and termination (UniProt P54785). It serves as a vital scaffold for the recruitment of chromatin-modifying enzymes that catalyze histone H2B monoubiquitination and H3K4/H3K79 methylation, marks associated with active transcription (NCBI Gene: 54623). In oncology, PAF1 is recognized as an oncogene, often overexpressed in pancreatic ductal adenocarcinoma, breast cancer, and ovarian cancer, where it promotes cell proliferation and maintains cancer stem cell populations (Dey et al., 2020). Beyond its role in cancer, PAF1 is involved in modulating host cell responses to viral infections and is utilized by viruses like HIV-1 to facilitate their own transcription (PubMed: 24336214). While there are currently no FDA-approved therapies targeting PAF1, experimental approaches including small molecule inhibitors of the PAF1 complex and PROTAC-mediated degradation are being explored as potential anti-cancer strategies (Monaghan et al., 2023). Its critical role in global gene expression suggests that therapeutic targeting must carefully balance efficacy against potential systemic toxicity (PubMed: 32156745).

Other names

PAF1 homologPancreatic differentiation 2PD2PAF1LRNA polymerase II-associated factor 1 homolog

Disruption of the PAF1 complex assembly or its recruitment to RNA polymerase II, or targeted proteasomal degradation of the PAF1 protein via proteolysis-targeting chimeras (PROTACs).