PD2/PAF1 at the Crossroads of the Cancer Network
| Autor: | Moorthy P. Ponnusamy, Surinder K. Batra, Arokia Priyanka Vaz, Parama Dey, Sukesh R. Bhaumik, Saswati Karmakar |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Carcinogenesis RNA polymerase II Biology Article 03 medical and health sciences Cancer stem cell Neoplasms Pancreatic cancer medicine Humans Neoplastic transformation Transcription factor Regulation of gene expression Nuclear Proteins musculoskeletal system medicine.disease Embryonic stem cell Cell biology Gene Expression Regulation Neoplastic 030104 developmental biology Oncology biology.protein Stem cell Transcription Factors |
| Zdroj: | Cancer Research. 78:313-319 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | 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. Cancer Res; 78(2); 313–9. ©2018 AACR. |
| Databáze: | OpenAIRE |
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