PD2/PAF1 at the crossroads of the cancer network

Saswati Karmakar, Parama Dey, Arokia P. Vaz, Sukesh R. Bhaumik, Moorthy P. Ponnusamy, Surinder K. Batra

Research output: Contribution to journalReview articlepeer-review

9 Scopus citations

Abstract

Pancreatic differentiation 2 (PD2)/RNA polymerase II–associated factor 1 (PAF1) is the core subunit of the human PAF1 complex (PAF1C) that regulates the promoter-proximal pausing of RNA polymerase II as well as transcription elongation and mRNA processing and coordinates events in mRNA stability and quality control. As an integral part of its transcription-regulatory function, PD2/PAF1 plays a role in posttranslational histone covalent modifications as well as regulates expression of critical genes of the cell-cycle machinery. PD2/PAF1 alone, and as a part of PAF1C, provides distinct roles in the maintenance of self-renewal of embryonic stem cells and cancer stem cells, and in lineage differentiation. Thus, PD2/PAF1 malfunction or its altered abundance is likely to affect normal cellular functions, leading to disease states. Indeed, PD2/PAF1 is found to be upregulated in poorly differentiated pancreatic cancer cells and has the capacity for neoplastic transformation when ectopically expressed in mouse fibroblast cells. Likewise, PD2/PAF1 is upregulated in pancreatic and ovarian cancer stem cells. Here, we concisely describe multifaceted roles of PD2/PAF1 associated with oncogenic transformation and implicate PD2/PAF1 as an attractive target for therapeutic development to combat malignancy.

Original languageEnglish (US)
Pages (from-to)313-319
Number of pages7
JournalCancer Research
Volume78
Issue number2
DOIs
StatePublished - Jan 15 2018

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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