P53 activates transcription by directing structural shifts in Mediator

Meyer K, Lin S, Bernecky C, Gao Y, Taatjes D. 2010. P53 activates transcription by directing structural shifts in Mediator. Nature Structural and Molecular Biology. 17(6), 753–760.


Journal Article | Published | English
Author
Meyer, Krista; Lin, Shih; Bernecky, CarrieIST Austria ; Gao, Yuefeng; Taatjes, Dylan
Abstract
It is not well understood how the human Mediator complex, transcription factor IIH and RNA polymerase II (Pol II) work together with activators to initiate transcription. Activator binding alters Mediator structure, yet the functional consequences of such structural shifts remain unknown. The p53 C terminus and its activation domain interact with different Mediator subunits, and we find that each interaction differentially affects Mediator structure; strikingly, distinct p53-Mediator structures differentially affect Pol II activity. Only the p53 activation domain induces the formation of a large pocket domain at the Mediator-Pol II interaction site, and this correlates with activation of stalled Pol II to a productively elongating state. Moreover, we define a Mediator requirement for TFIIH-dependent Pol II C-terminal domain phosphorylation and identify substantial differences in Pol II C-terminal domain processing that correspond to distinct p53-Mediator structural states. Our results define a fundamental mechanism by which p53 activates transcription and suggest that Mediator structural shifts trigger activation of stalled Pol II complexes.
Publishing Year
Date Published
2010-06-01
Journal Title
Nature Structural and Molecular Biology
Volume
17
Issue
6
Page
753 - 760
IST-REx-ID
598

Cite this

Meyer K, Lin S, Bernecky C, Gao Y, Taatjes D. P53 activates transcription by directing structural shifts in Mediator. Nature Structural and Molecular Biology. 2010;17(6):753-760. doi:10.1038/nsmb.1816
Meyer, K., Lin, S., Bernecky, C., Gao, Y., & Taatjes, D. (2010). P53 activates transcription by directing structural shifts in Mediator. Nature Structural and Molecular Biology. Nature Publishing Group. https://doi.org/10.1038/nsmb.1816
Meyer, Krista, Shih Lin, Carrie Bernecky, Yuefeng Gao, and Dylan Taatjes. “P53 Activates Transcription by Directing Structural Shifts in Mediator.” Nature Structural and Molecular Biology. Nature Publishing Group, 2010. https://doi.org/10.1038/nsmb.1816.
K. Meyer, S. Lin, C. Bernecky, Y. Gao, and D. Taatjes, “P53 activates transcription by directing structural shifts in Mediator,” Nature Structural and Molecular Biology, vol. 17, no. 6. Nature Publishing Group, pp. 753–760, 2010.
Meyer K, Lin S, Bernecky C, Gao Y, Taatjes D. 2010. P53 activates transcription by directing structural shifts in Mediator. Nature Structural and Molecular Biology. 17(6), 753–760.
Meyer, Krista, et al. “P53 Activates Transcription by Directing Structural Shifts in Mediator.” Nature Structural and Molecular Biology, vol. 17, no. 6, Nature Publishing Group, 2010, pp. 753–60, doi:10.1038/nsmb.1816.
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