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Science 296 (5568): 755-758

Copyright © 2002 by the American Association for the Advancement of Science

Transcription Control by E1A and MAP Kinase Pathway via Sur2 Mediator Subunit

Jennitte L. Stevens,1 Greg T. Cantin,1 Gang Wang,1 Andrej Shevchenko,2 Anna Shevchenko,2 Arnold J. Berk13*

Sur2 is a metazoan Mediator subunit that interacts with the adenovirus E1A protein and functions in a mitogen-activated protein kinase pathway required for vulva development in Caenorhabditis elegans. We generated sur2-/- embryonic stem cells to analyze its function as a mammalian Mediator component. Our results show that Sur2 forms a subcomplex of the Mediator with two other subunits, TRAP/Med100 and 95. Knock-out of Sur2 prevents activation by E1A-CR3 and the mitogen-activated protein kinase-regulated ETS transcription factor Elk-1, but not by multiple other transcription factors. These results imply that specific activation domains stimulate transcription by binding to distinct Mediator subunits. Activation by E1A and Elk-1 requires recruitment of Mediator to a promoter by binding to its Sur2 subunit.

1 Molecular Biology Institute, University of California, Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA.
2 Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
3 Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
*   To whom correspondence should be addressed. E-mail: berk{at}

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The ETS Domain Transcription Factor Elk-1 Regulates the Expression of Its Partner Protein, SRF.
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Requirement of Sur2 for Efficient Replication of Mouse Adenovirus Type 1.
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J. Virol. 78, 12888-12900
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Structural and Functional Organization of TRAP220, the TRAP/Mediator Subunit That Is Targeted by Nuclear Receptors.
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MED16 and MED23 of Mediator are coactivators of lipopolysaccharide- and heat-shock-induced transcriptional activators.
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PNAS 101, 12153-12158
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J. Biol. Chem. 279, 29270-29277
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Role of Mediator in Transcriptional Activation by the Aryl Hydrocarbon Receptor.
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   Abstract »    Full Text »    PDF »
The activator-recruited cofactor/Mediator coactivator subunit ARC92 is a functionally important target of the VP16 transcriptional activator.
F. Yang, R. DeBeaumont, S. Zhou, and A. M. Naar (2004)
PNAS 101, 2339-2344
   Abstract »    Full Text »    PDF »
A novel docking site on Mediator is critical for activation by VP16 in mammalian cells.
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J. Virol. 77, 11006-11015
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Activation domain-mediator interactions promote transcription preinitiation complex assembly on promoter DNA.
G. T. Cantin, J. L. Stevens, and A. J. Berk (2003)
PNAS 100, 12003-12008
   Abstract »    Full Text »    PDF »
The mediator coactivator complex: functional and physical roles in transcriptional regulation.
B. A. Lewis and D. Reinberg (2003)
J. Cell Sci. 116, 3667-3675
   Abstract »    Full Text »    PDF »
Human Mediator Enhances Activator-Facilitated Recruitment of RNA Polymerase II and Promoter Recognition by TATA-Binding Protein (TBP) Independently of TBP-Associated Factors.
S.-Y. Wu, T. Zhou, and C.-M. Chiang (2003)
Mol. Cell. Biol. 23, 6229-6242
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Two subunits of the Drosophila mediator complex act together to control cell affinity.
F. Janody, Z. Martirosyan, A. Benlali, and J. E. Treisman (2003)
Development 130, 3691-3701
   Abstract »    Full Text »    PDF »
Principal Role of TRAP/Mediator and SWI/SNF Complexes in Kaposi's Sarcoma-Associated Herpesvirus RTA-Mediated Lytic Reactivation.
Y. Gwack, H. J. Baek, H. Nakamura, S. H. Lee, M. Meisterernst, R. G. Roeder, and J. U. Jung (2003)
Mol. Cell. Biol. 23, 2055-2067
   Abstract »    Full Text »    PDF »
Signal-Induced Transcriptional Activation by Dif Requires the dTRAP80 Mediator Module.
J. M. Park, J. M. Kim, L. K. Kim, S. N. Kim, J. Kim-Ha, J. H. Kim, and Y.-J. Kim (2003)
Mol. Cell. Biol. 23, 1358-1367
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External control of Her2 expression and cancer cell growth by targeting a Ras-linked coactivator.
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PNAS 99, 12747-12752
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In Vivo Association of Adenovirus Large E1A Protein with the Human Mediator Complex in Adenovirus-Infected and -Transformed Cells.
G. Wang and A. J. Berk (2002)
J. Virol. 76, 9186-9193
   Abstract »    Full Text »    PDF »
Broad Requirement for the Mediator Subunit RGR-1 for Transcription in the Caenorhabditis elegans Embryo.
E. Y. Shim, A. K. Walker, and T. K. Blackwell (2002)
J. Biol. Chem. 277, 30413-30416
   Abstract »    Full Text »    PDF »
SOX9 interacts with a component of the human thyroid hormone receptor-associated protein complex.
R. Zhou, N. Bonneaud, C.-X. Yuan, P. de Santa Barbara, B. Boizet, S. Tibor, G. Scherer, R. G. Roeder, F. Poulat, and P. Berta (2002)
Nucleic Acids Res. 30, 3245-3252
   Abstract »    Full Text »    PDF »
C. elegans EOR-1/PLZF and EOR-2 positively regulate Ras and Wnt signaling and function redundantly with LIN-25 and the SUR-2 Mediator component.
R. M. Howard and M. V. Sundaram (2002)
Genes & Dev. 16, 1815-1827
   Abstract »    Full Text »    PDF »
The TRAP100 component of the TRAP/Mediator complex is essential in broad transcriptional events and development.
M. Ito, H. J. Okano, R. B. Darnell, and R. G. Roeder (2002)
EMBO J. 21, 3464-3475
   Abstract »    Full Text »    PDF »

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