Ubiquitin-Proteasome System Regulation of an Evolutionarily Conserved RNA Polymerase II-Associated Factor 1 Involved in Pancreatic Oncogenesis

Biochemistry. 2017 Nov 21;56(46):6083-6086. doi: 10.1021/acs.biochem.7b00865. Epub 2017 Oct 19.


The evolutionarily conserved RNA polymerase II-associated factor 1 (Paf1) from yeast to humans regulates transcription and associated processes, and thus, malfunctions and/or misregulations of Paf1 are associated with cellular pathologies. Indeed, Paf1 (also known as PD2 or pancreatic differentiation 2) is found to be upregulated in poorly differentiated cancer cells, and such upregulation is involved in cellular transformation or oncogenesis. However, the basis for Paf1 upregulation in these cells remains largely unknown. In light of this, we have tested here the idea that the ubiquitin-proteasome system (UPS) regulates the cellular abundance of Paf1. In this direction, we analyzed the role of UPS in regulation of Paf1's abundance in yeast. We find that Paf1 undergoes ubiquitylation and is degraded by the 26S proteasome in yeast, thus deciphering UPS regulation of an evolutionarily conserved factor, Paf1, involved in various cellular processes at the crossroads of the cancer networks. Likewise, Paf1 undergoes proteasomal degradation in well-differentiated, but not poorly differentiated, pancreatic cancer cells, hence pointing to the UPS in upregulation of Paf1 in poorly differentiated cancers. Collectively, our results reveal UPS regulation of Paf1 and suggest downregulation of UPS in elevating Paf1's abundance in poorly differentiated cancers.

MeSH terms

  • Carcinogenesis / metabolism*
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Humans
  • Nuclear Proteins / metabolism*
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteolysis
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Transcription Factors
  • Ubiquitin / metabolism*
  • Ubiquitination


  • Nuclear Proteins
  • PAF1 protein, S cerevisiae
  • PAF1 protein, human
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Ubiquitin
  • Proteasome Endopeptidase Complex