The Role of p53-dependent Histone mRNA Processing in the Development of Cancer

• Applicant: Professor Dr. Steven Johnsen, Ph.D.
• Subject Area: Hematology, Oncology
• Term: from 2009 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 149096498

Mutation or deletion of p53 is a frequent occurrence and is essential for the development and progression of many types of cancer. One of the primary roles of p53 is the regulation of gene expression. Recent studies uncovered that changes in mRNA processing are also a hallmark of cancer. However, if p53 influences mRNA processing and whether this is important for the development and/or progression of cancer remains unknown. In the proposed project we will examine the role of p53 in controlling replication-dependent histone gene transcription and mRNA 3’ end processing. These studies will build upon our previous and preliminary work showing that specific signaling molecules and chromatin modifications are essential for maintaining proper replication-dependent histone mRNA processing. In this application we will specifically investigate: (1) the regulation of histone mRNA processing by p53 including the role of downstream p53 targets and specific signaling molecules and chromatin modifications, (2) the effects of mutant p53 on histone mRNA 3’ end processing, (3) the biological role of polyadenylated replication-dependent histone mRNA transcripts and (4) the expression of p53, the transcription factor NPAT, and histone mRNA polyadenylation in primary tumors and metastases.

• DFG Programme: Research Grants