Recommended Readings: Robert G. Roeder, Ph.D., April 13

Monday Lecture Series
Monday, April 13, 2015
4:00 p.m., Carson Family Auditorium (CRC)

Robert G. Roeder, Ph.D.
Arnold and Mabel Beckman Professor and Head,
Laboratory of Biochemistry and Molecular Biology,
The Rockefeller University

Transcriptional Regulatory Mechanisms in Animal Cells

Recommended Readings

Empirical Articles

Jiang, H., Lu, X., Shimada, M., Dou, Y., Tang, Z., & Roeder, R. G. (2013). Regulation of transcription by the MLL2 complex and MLL complex–associated AKAP95. Nature Structural & Molecular Biology, 20(10), 1156-1163. doi:10.1038/nsmb.2656

Sabari, B. R., Tang, Z., Huang, H., Yong-Gonzalez, V., Molina, H., Kong, H. E., … & Allis, C. D. (2015). Intracellular crotonyl-CoA stimulates transcription through p300-catalyzed histone crotonylation. Molecular Cell. doi:10.1016/j.molcel.2015.02.029

Zhang, P., Tu, B., Wang, H., Cao, Z., Tang, M., Zhang, C., … & Zhu, W. G. (2014). Tumor suppressor p53 cooperates with SIRT6 to regulate gluconeogenesis by promoting FoxO1 nuclear exclusion. Proceedings of the National Academy of Sciences, 111(29), 10684-10689. doi:10.1073/pnas.1411026111

Review Papers

Malik, S., & Roeder, R. G. (2010). The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation. Nature Reviews Genetics, 11(11), 761-772. doi:10.1038/nrg2901

Roeder, R. G. (2005). Transcriptional regulation and the role of diverse coactivators in animal cells. FEBS letters, 579(4), 909-915. doi:10.1016/j.febslet.2004.12.007

Expanding the horizon of chemotherapeutic targets: From MDM2 to MDMX (MDM4)

Antonio Macchiarulo, Nicola Giacchè, Andrea Carotti, Fabiola Moretti and Roberto Pellicciari

DOI: 10.1039/C0MD00238K

Alterations of p53 signalling pathway is the most frequent event in human cancers. About 50% of these, albeit showing wild-type p53, have flaws in the control mechanisms of p53 levels and activity. MDM2 and MDMX (MDM4) are the main negative regulators of p53. The relevance of MDM2 on the regulation of p53 levels and activity has fostered the development of strategies aimed at restoring p53 functions by blocking the physical interaction between MDM2 and p53. As a consequence, a number of different small molecules and peptidomimetics have been disclosed in the last decade as inhibitors of MDM2/p53 interaction. Recent studies, however, have thrust MDMX into the limelight as an additional chemotherapeutic target, suggesting the presence of a more complex relationship between MDM2, MDMX and p53. In this review article, we report key aspects of MDMX-mediated regulation of p53, recent advances in the structural characterization of the protein, and the progress made so far in the medicinal chemistry of MDMX ligands.