Unraveling p300/CBP oncogenic signaling utilizing small molecule inhibitors and probes

• Applicant: Dr. André Richters
• Subject Area: Biological and Biomimetic Chemistry ; Biochemistry
• Term: from 2015 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 276707199

This research proposal aims to develop a robust and cost-efficient biochemical assay to identify inhibitors and ligands for the histone acetyltransferases (HATs) p300 and CBP. Furthermore, high throughput screens using chemically diverse compound libraries will be performed in an effort to identify potent small molecule HAT inhibitors. The ultimate goal is to develop effective and specific HAT inhibitors and tool compounds to probe their potential to inhibit the biological activity of p300/CBP target oncogenes by affecting their stability and inducing their enhanced degradation. In particular, it is desired to discover ligands which may disrupt the HAT-mediated c-Myc activation in order to decipher the oncogenic interactions within the c-Myc interactome using multiple cancer cell lines (e.g., prostate cancer and melanoma). If applicable further investigations with respect to the potential use of these molecules as anticancer agents in animal models are intended. This research approach will also investigate the potential use of HAT inhibitors in inhibiting other acetylation-dependent oncogenic transcription factors such as androgen and estrogen receptors, which can lead to broad applications in cancer research.This research has the potential to uncover small molecule p300/CBP inhibitors to further understand the biological impact of HAT activity in tumor development as well as in understanding the role of acetylation in the tumorigenicity of known transcription factor oncogenes.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Angela Koehler, Ph.D.