Premium
Regulation of an Evolutionarily Conserved RNA Polymerase II‐Associated Factor 1 (Paf1) Involved in Pancreatic Oncogenesis
Author(s) -
Barman Priyanka,
Ferdoush Jannatul,
Kaja Amala,
Karmakar Saswati,
Uprety Bhawana,
Batra Surinder K.,
Bhaumik Sukesh R.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.648.8
Subject(s) - downregulation and upregulation , transcription factor , biology , microbiology and biotechnology , transcription (linguistics) , rna polymerase ii , carcinogenesis , gene expression , gene , genetics , promoter , linguistics , philosophy
The multifunctional RNA polymerase II‐associated factor (Paf1) is highly conserved from yeast to humans and plays an important role in regulation of transcription and its associated processes. Hence, malfunctions and/or misregulations of Paf1 are associated with cellular pathologies. Recent studies found that Paf1 (also known as PD2 or pancreatic differentiation 2) is 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. Thus, our results reveal UPS regulation of Paf1 and suggest downregulation of UPS in elevating Paf1's abundance in poorly differentiated cancers. Further, we find that misregulation of Paf1's abundance alters transcription. Collectively, our results demonstrate that Paf1 is regulated by UPS to control transcription, thus providing a new regulatory mechanism of gene expression. Support or Funding Information NIH‐2R15GM088798‐02 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .