An hsRPB4/7-dependent yeast assay for trans-activation by the EWS oncogene

Oncogene
H Zhou, K A Lee

Abstract

Chromosomal fusions of the N-terminal region of the Ewings Sarcoma Oncogene (EWS-Activation-Domain, EAD) to the DNA-binding domains of a variety of cellular transcription factors, produce oncogenic proteins (EWS-fusion proteins (EFPs)) that cause a variety of malignancies. The EAD can act as a potent transcriptional activation domain and is required for the oncogenic activity of EFPs. Previous studies demonstrating a physical interaction between the EAD and the human RNA Polymerase II subunit hsRPB7 suggest a crucial role for RPB7 and its partner, RPB4, in EAD function. Homologues of hsRPB4/7 exist in S. cerevisiae, and here we describe an RPB4/7-dependent yeast assay for EAD-mediated trans-activation. Conditional yeast strains lacking RPB4 are defective for trans-activation by a Gal4/EAD fusion protein at the permissive temperature. Introduction of hsRPB4 alone is unable to rescue trans-activation, while a combination of hsRPB4 and hsRPB7 significantly rescues activity. These findings provide the first functional evidence for a direct role of the RPB4/7 complex in EAD-mediated trans-activation. In addition, the yeast assay provides a tractable system for further molecular analysis of EAD and RPB4/7 action.

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Citations

Sep 29, 2009·Journal of Molecular Cell Biology·Adelene Y Tan, James L Manley
Mar 4, 2005·Nucleic Acids Research·Deepa Alex, Kevin A W Lee
Nov 12, 2005·Nucleic Acids Research·Hedije MekaPeter Brick
Jul 20, 2002·Current Opinion in Oncology·Jeannette L Bennicelli, Frederic G Barr
Dec 3, 2011·Sarcoma·David Herrero-MartinDave N T Aryee
Jan 5, 2007·Proceedings of the National Academy of Sciences of the United States of America·King Pan NgKevin A W Lee
May 15, 2003·Proceedings of the National Academy of Sciences of the United States of America·David A Bushnell, Roger D Kornberg
Oct 2, 2013·International Journal of Cell Biology·Maria Paola Paronetto
Feb 18, 2015·BioMed Research International·Roumiana Todorova
Jan 5, 2011·Protein & Cell·King Pan NgKevin A W Lee
Feb 6, 2016·Oncotarget·Emily R TheisenStephen L Lessnick

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