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The human homologue of the RNA polymerase II-associated factor 1 (hPaf1), localized on the 19q13 amplicon, is associated with tumorigenesis

Oncogene volume 25, pages 3247–3257 (2006)Cite this article

Abstract

The 19q13 amplicon in pancreatic cancer cells contains a novel pancreatic differentiation 2 (PD2) gene (accession number AJ401156), which was identified by differential screening analysis. PD2 is the human homologue of the RNA polymerase II-associated factor 1 (hPaf1). In yeast, Paf1 is part of the transcription machinery, acting as a docking protein in between the complexes Rad6-Bre1, COMPASS-Dot1p, and the phosphorylated carboxyl terminal domain of the RNA polymerase II. As such, Paf1 is directly involved in transcription elongation via histone H2B ubiquitination and histone H3 methylation. The PD2 sequence is highly conserved from Drosophila to humans with up to 98% identity between rodent and human, suggesting the functional importance of PD2/hPaf1 to maintain cellular homeostasis. PD2 is a modular protein composed of RNA recognition motif, DEAD-boxes, an aspartic/serine (DS)-domain, a regulator of the chromosome condensation domain and myc-type helix–loop–helix domains. Our results further showed that PD2 is a nuclear 80 kDa protein, which interacts with RNA polymerase II. In addition, we have demonstrated that the overexpression of PD2 in the NIH 3T3 cells result in enhanced growth rates in vitro and tumor formation in vivo. Altogether, this paper presents strong evidence that the overexpression of PD2/hPaf1 is involved in cancer development.

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Abbreviations

PD2:

pancreatic differentiation 2

Paf1:

RNA polymerase II-associated factor

HLH:

helix–loop–helix

cAMP:

cyclic adenosine monophosphate

kb:

kilobase

bp:

base pair

PCR:

polymerase chain reaction

CGH:

comparative genomic hybridization

RRM:

eukaryotic RNA recognition motif

RCC1:

regulator of chromosome condensation domain

RNAPII:

RNA polymerase II

GTFs:

general transcription factors

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Acknowledgements

The work reported in this manuscript was initiated in the late 1980s by Drs Batra and Hollingsworth under the direction and sponsorship of Professor Richard S Metzgar (Duke University Medical Center, NC, USA), whom authors gratefully acknowledge for his thoughtful and scholarly insights, exemplary leadership, generous support and lasting friendship. We would like to thank Mr Jason Jokerst for making mouse monoclonal antibodies, Mr Erik Moore for technical assistance, the Molecular Biology Core Facility, UNMC, for oligonucleotide synthesis and DNA sequencing, Monoclonal Antibody Core Facility for making antibodies and Ms Kristi LW Berger for editorial assistance. Dr Nemos acknowledges the Travel Award Fellowship from the American/French Philippe Foundation. This work was supported, in part, by grants from the NIH (CA78590 and CA72712).

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  1. N Moniaux and C Nemos: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA

    N Moniaux, C Nemos, S C Chauhan, S Deb, A Choudhury, M A Hollingsworth & S K Batra

  2. Eppley Institute, University of Nebraska Medical Center, Omaha, NE, USA

    B M Schmied, K Morikane, M VanLith, M Sutherlin, M A Hollingsworth & S K Batra

  3. Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO, USA

    J M Sikela

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  1. N Moniaux
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Correspondence to S K Batra.

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Moniaux, N., Nemos, C., Schmied, B. et al. The human homologue of the RNA polymerase II-associated factor 1 (hPaf1), localized on the 19q13 amplicon, is associated with tumorigenesis. Oncogene 25, 3247–3257 (2006). https://doi.org/10.1038/sj.onc.1209353

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